@sjcrh/proteinpaint-server 2.18.0 → 2.19.0

This diff represents the content of publicly available package versions that have been released to one of the supported registries. The information contained in this diff is provided for informational purposes only and reflects changes between package versions as they appear in their respective public registries.
Files changed (13) hide show
  1. package/cards/bam.json +1 -1
  2. package/cards/dnanexusTips.txt +10 -10
  3. package/cards/exprank.json +1 -1
  4. package/cards/genomepaint.json +1 -1
  5. package/cards/index.json +25 -27
  6. package/cards/junction.json +4 -4
  7. package/cards/pgv.json +1 -1
  8. package/cards/singlecell.json +1 -1
  9. package/cards/study.json +1 -1
  10. package/cards/svview.txt +5 -5
  11. package/cards/tklist.json +1 -1
  12. package/package.json +1 -1
  13. package/server.js +1 -1
package/server.js CHANGED
@@ -1 +1 @@
1
- (()=>{var t={4052:(t,e,n)=>{"use strict";n.r(e),n.d(e,{schemeCategory20:()=>r});const r=["#1f77b4","#aec7e8","#ff7f0e","#ffbb78","#2ca02c","#98df8a","#d62728","#ff9896","#9467bd","#c5b0d5","#8c564b","#c49c94","#e377c2","#f7b6d2","#7f7f7f","#c7c7c7","#bcbd22","#dbdb8d","#17becf","#9edae5"]},6733:(t,e,n)=>{"use strict";n.r(e),n.d(e,{parseheader:()=>i,parseline:()=>s});var r=n(2273),o=n(8064);function i(t,e){const n=t.toLowerCase().split("\t");if(n.length<=1)return"invalid file header for CNV";const r=(...t)=>{for(const e of t){const t=n.indexOf(e);if(-1!=t)return t}return-1};let o=r("gene");return-1==o?"gene missing from header":(n[o]="gene",o=r("cnv"),-1==o?"CNV missing from header":(n[o]="cnv",o=r("sample","sample_name","tumor_sample_barcode"),-1!=o&&(n[o]="sample"),o=r("patient","donor","target_case_id"),-1!=o&&(n[o]="patient"),o=r("disease"),-1!=o&&(n[o]="disease"),o=r("origin"),-1!=o&&(n[o]="origin"),o=r("sampletype","sample type","sample_type"),-1!=o&&(n[o]="sampletype"),e.cnv.header=n,e.cnv.loaded=!0,!1))}function s(t,e,n){if(""==e||"#"==e[0])return;const i=e.split("\t"),s={};for(let t=0;t<n.cnv.header.length;t++)s[n.cnv.header[t]]=i[t];if(!s.gene)return void n.cnv.badlines.push([t,"missing gene",i]);if(!s.cnv)return void n.cnv.badlines.push([t,"missing cnv value",i]);switch(s.cnv.toLowerCase()){case"amplification":case"gain":s.class=r.mclasscnvgain;break;case"deletion":case"loss":s.class=r.mclasscnvloss;break;case"loh":s.class=r.mclasscnvloh;break;default:n.cnv.badlines.push([t,"invalid cnv value: "+s.cnv,i]),s.class=null}if(!s.class)return;if(o.parsesample(s,n,t,i,n.cnv.badlines))return;s.dt=r.dtcnv,n.good++;const a=n.geneToUpper?s.gene.toUpperCase():s.gene;a in n.data||(n.data[a]=[]),n.data[a].push(s)}},5558:(t,e,n)=>{"use strict";n.r(e),n.d(e,{parseheader:()=>i,parseline:()=>s});var r=n(2273),o=n(8064);function i(t,e){const n=t.toLowerCase().split("\t");if(n.length<=1)return"invalid header line for intragenic deletion";const r=(...t)=>{for(const e of t){const t=n.indexOf(e);if(-1!=t)return t}return-1};let o=r("gene");if(-1==o)return"gene missing from header";if(n[o]="gene",o=r("annovar_isoform","mrna_accession","mrna accession","refseq_mrna_id","annovar_sj_filter_isoform","refseq","isoform"),-1==o)return"isoform missing from header";if(n[o]="isoform",o=r("rnaposition"),-1!=o){if(n[o]="rnaposition",o=r("rnadellength"),-1==o)return"rnadellength is required when rnaPosition is used";n[o]="rnadellength"}if(o=r("chromosome","chr"),-1!=o){if(n[o]="chr",o=r("chr_start"),-1==o)return"chr_start is required when chr is used";if(n[o]="chrpos1",o=r("chr_stop"),-1==o)return"chr_stop is required when chr is used";n[o]="chrpos2"}return o=r("sample","sample_name","tumor_sample_barcode"),-1!=o&&(n[o]="sample"),o=r("patient","donor","target_case_id"),-1!=o&&(n[o]="patient"),o=r("disease"),-1!=o&&(n[o]="disease"),o=r("origin"),-1!=o&&(n[o]="origin"),o=r("sampletype","sample type","sample_type"),-1!=o&&(n[o]="sampletype"),e.del.header=n,e.del.loaded=!0,!1}function s(t,e,n){if(""==e||"#"==e[0])return;const i=e.split("\t"),s={};for(let t=0;t<n.del.header.length&&null!=i[t];t++)s[n.del.header[t]]=i[t];if(s.gene){if(s.rnaposition){let e=Number.parseInt(s.rnaposition);if(Number.isNaN(e)||e<0)return void n.del.badlines.push([t,"invalid rnaPosition value",i]);if(s.rnaposition=e,!s.rnadellength)return void n.del.badlines.push([t,"missing rnaDellength value",i]);if(e=Number.parseInt(s.rnadellength),Number.isNaN(e)||e<0)return void n.del.badlines.push([t,"invalid rnaDellength value",i]);s.rnadellength=e}if(s.chr){let e=Number.parseInt(s.chrpos1);if(Number.isNaN(e)||e<0)return void n.del.badlines.push([t,"invalid chr_start value",i]);if(s.chrpos1=e,e=Number.parseInt(s.chrpos2),Number.isNaN(e)||e<0)return void n.del.badlines.push([t,"invalid chr_stop value",i]);s.chrpos2=e}if(!o.parsesample(s,n,t,i,n.del.badlines)){s.dt=r.dtdel,s.class=r.mclassdel,s.mname="DEL",n.good++;var a=n.geneToUpper?s.gene.toUpperCase():s.gene;a in n.data||(n.data[a]=[]),n.data[a].push(s)}}else n.del.badlines.push([t,"missing gene",i])}},3602:(t,e,n)=>{"use strict";n.r(e),n.d(e,{parseheader:()=>i,parseline:()=>s});var r=n(2273),o=n(8064);function i(t,e){const n=t.toLowerCase().split("\t");if(n.length<=1)return"invalid header line for ITD";const r=(...t)=>{for(const e of t){const t=n.indexOf(e);if(-1!=t)return t}return-1};let o=r("gene");if(-1==o)return"gene missing from header";if(n[o]="gene",o=r("annovar_isoform","mrna_accession","mrna accession","refseq_mrna_id","annovar_sj_filter_isoform","refseq","isoform"),-1==o)return"isoform missing from header";if(n[o]="isoform",o=r("rnaposition"),-1!=o){if(n[o]="rnaposition",o=r("rnaduplength"),-1==o)return"rnaduplength is required when rnaposition is present";n[o]="rnaduplength"}if(o=r("chromosome","chr"),-1!=o){if(n[o]="chr",o=r("chr_start"),-1==o)return"chr_start is required when chr is present";if(n[o]="chrpos1",o=r("chr_stop"),-1==o)return"chr_stop is required when chr is present";n[o]="chrpos2"}return o=r("sample","sample_name","tumor_sample_barcode"),-1!=o&&(n[o]="sample"),o=r("patient","donor","target_case_id"),-1!=o&&(n[o]="patient"),o=r("disease"),-1!=o&&(n[o]="disease"),o=r("origin"),-1!=o&&(n[o]="origin"),o=r("sampletype","sample type","sample_type"),-1!=o&&(n[o]="sampletype"),e.itd.header=n,e.itd.loaded=!0,!1}function s(t,e,n){if(""==e||"#"==e[0])return;const i=e.split("\t"),s={};for(let t=0;t<n.itd.header.length&&null!=i[t];t++)s[n.itd.header[t]]=i[t];if(s.gene){if(s.rnaposition){let e=Number.parseInt(s.rnaposition);if(Number.isNaN(e)||e<0)return void n.itd.badlines.push([t,"invalid rnaPosition value",i]);if(s.rnaposition=e,!s.rnaduplength)return void n.itd.badlines.push([t,"missing rnaDuplength value",i]);if(e=Number.parseInt(s.rnaduplength),Number.isNaN(e)||e<0)return void n.itd.badlines.push([t,"invalid rnaDuplength value",i]);s.rnaduplength=e}if(s.chr){let e=Number.parseInt(s.chrpos1);if(Number.isNaN(e)||e<0)return void n.itd.badlines.push([t,"invalid chr_start value",i]);if(s.chrpos1=e,e=Number.parseInt(s.chrpos2),Number.isNaN(e)||e<0)return void n.itd.badlines.push([t,"invalid chr_stop value",i]);s.chrpos2=e}if(!o.parsesample(s,n,t,i,n.itd.badlines)){s.dt=r.dtitd,s.class=r.mclassitd,s.mname="ITD",n.good++;var a=n.geneToUpper?s.gene.toUpperCase():s.gene;a in n.data||(n.data[a]=[]),n.data[a].push(s)}}else n.itd.badlines.push([t,"missing gene",i])}},8064:(t,e,n)=>{"use strict";n.r(e),n.d(e,{default:()=>o,init_bulk_flag:()=>i,parsesample:()=>s});var r=n(2273);const o={};function i(t){if(!t)return null;const e={};for(const t in r.mclass)e[r.mclass[t].label.toUpperCase()]=t;return{genome:t,mclasslabel2key:e,data:{},sample2disease:{},patient2st:{},good:0,geneToUpper:!0,snv:{loaded:!1,header:null,badlines:[],missense:0,silent:0},svjson:{loaded:!1,header:null,badlines:[]},fusion:{loaded:!1,header:null,badlines:[],original:[]},sv:{loaded:!1,header:null,badlines:[],original:[]},cnv:{loaded:!1,header:null,badlines:[]},itd:{loaded:!1,header:null,badlines:[]},del:{loaded:!1,header:null,badlines:[]},truncation:{loaded:!1,header:null,badlines:[]}}}function s(t,e,n,o,i){let s=r.moriginsomatic;if(t.sampletype){switch(t.sampletype.toLowerCase()){case"relapse":s=r.moriginrelapse;break;case"germline":s=r.morigingermline}t.sample?t.patient||(t.patient=t.sample+" "+t.sampletype):t.patient&&(t.sample=t.patient+" "+t.sampletype)}else t.patient?t.sample?t.sampletype=t.sample:t.sample=t.sampletype=t.patient:t.sample&&(t.sampletype=t.sample);if(t.origin){switch(t.origin.toLowerCase()){case"r":case"relapse":s=r.moriginrelapse,t.isrim2=!0;break;case"g":case"germline":s=r.morigingermline,t.isrim1=!0;break;case"gp":case"germline pathogenic":s=r.morigingermlinepathogenic,t.isrim1=!0;break;case"gnp":case"germline nonpathogenic":case"germline non-pathogenic":s=r.morigingermlinenonpathogenic,t.isrim1=!0;break;case"s":case"somatic":case"diagnosis":s=r.moriginsomatic}}if(t.origin=s,!t.sample&&!t.patient)return;const a="no patient/individual name";if(t.patient?(e.patient2st[t.patient]||(e.patient2st[t.patient]={}),e.patient2st[t.patient][t.sampletype]=t.sample):(e.patient2st[a]||(e.patient2st[a]={}),e.patient2st[a][t.sampletype]=t.sample),t.sample&&t.disease)if(t.sample in e.sample2disease){if(t.disease!=e.sample2disease[t.sample])return e.snv.badlines.push([n,'conflict of disease types for sample "'+t.sample+'": '+t.disease+", "+e.sample2disease[t.sample],o]),!0}else e.sample2disease[t.sample]=t.disease;return!1}},5494:(t,e,n)=>{"use strict";n.r(e),n.d(e,{parseheader:()=>i,parseline:()=>s});var r=n(2273),o=n(8064);function i(t,e){const n=t.toLowerCase().split("\t");if(n.length<=1)return"invalid file header for snv/indel";const r=(...t)=>{for(const e of t){const t=n.indexOf(e);if(-1!=t)return t}return-1};let o=r("annovar_gene","annovar_sj_gene","gene","genename","gene_symbol","hugo_symbol");return-1==o?"gene missing from header":(n[o]="gene",o=r("annovar_aachange","amino_acid_change","annovar_sj_aachange","aachange","protein_change","variant"),-1==o?"amino_acid_change missing from header":(n[o]="mname",o=r("annovar_class","class","mclass","variant_class","variant_classification","annovar_sj_class"),-1==o?"variant_class missing from header":(n[o]="class",o=r("chromosome","chr"),-1==o?"chromosome missing from header":(n[o]="chr",o=r("wu_hg19_pos","start","start_position","chr_position","position"),-1==o?"start missing from header":(n[o]="pos",o=r("annovar_isoform","mrna_accession","mrna accession","refseq_mrna_id","annovar_sj_filter_isoform","refseq","isoform"),-1==o?"isoform missing from header":(n[o]="isoform",o=r("sample","sample_name","tumor_sample_barcode"),-1!=o&&(n[o]="sample"),o=r("patient","donor","target_case_id"),-1!=o&&(n[o]="patient"),o=r("quantitative_measurements"),-1!=o&&(n[o]="qmset"),o=r("mutant_reads_in_case","mutant_in_tumor","tumor_readcount_alt"),-1!=o&&(n[o]="maf_tumor_v1"),o=r("total_reads_in_case","total_in_tumor","tumor_readcount_total"),-1!=o&&(n[o]="maf_tumor_v2"),o=r("mutant_reads_in_control","mutant_in_normal","normal_readcount_alt"),-1!=o&&(n[o]="maf_normal_v1"),o=r("total_reads_in_control","total_in_normal","normal_readcount_total"),-1!=o&&(n[o]="maf_normal_v2"),o=r("cdna_change"),-1!=o&&(n[o]="cdna_change"),o=r("sampletype","sample type","sample_type"),-1!=o&&(n[o]="sampletype"),o=r("origin"),-1!=o&&(n[o]="origin"),o=r("cancer","disease","diagnosis"),-1!=o&&(n[o]="disease"),e.snv.header=n,e.snv.loaded=!0,!1))))))}function s(t,e,n){if(""==e||"#"==e[0])return;const i=e.split("\t"),s={};for(let t=0;t<n.snv.header.length&&null!=i[t];t++)s[n.snv.header[t]]=i[t];if(!s.gene)return void n.snv.badlines.push([t,"missing gene",i]);if("UNKNOWN"==s.gene.toUpperCase())return void n.snv.badlines.push([t,"gene name is UNKNOWN",i]);if(!s.isoform)return void n.snv.badlines.push([t,"missing isoform",i]);if(s.mname)0==s.mname.indexOf("p.")&&(s.mname=s.mname.replace(/^p\./,""));else if(s.mname=s.cdna_change,!s.mname)return void n.snv.badlines.push([t,"missing amino acid change",i]);if(!s.class)return void n.snv.badlines.push([t,"missing mutation class",i]);let a=n.mclasslabel2key[s.class.toUpperCase()];if(a)s.class=a;else{if(a=r.mclasstester(s.class),!a)return void n.snv.badlines.push([t,"wrong mutation class: "+s.class,i]);s.class=a}if(o.parsesample(s,n,t,i,n.snv.badlines))return;if(!s.chr)return void n.snv.badlines.push([t,"missing chromosome",i]);if(0!=s.chr.toLowerCase().indexOf("chr")&&(s.chr="chr"+s.chr),!s.pos)return void n.snv.badlines.push([t,"missing chromosome position",i]);const l=Number.parseInt(s.pos);if(Number.isNaN(l))return void n.snv.badlines.push([t,"invalid chromosome position",i]);if(s.pos=l-1,null!=s.maf_tumor_v2&&null!=s.maf_tumor_v1){if(""==s.maf_tumor_v2);else{let e=Number.parseInt(s.maf_tumor_v1),r=Number.parseInt(s.maf_tumor_v2);if(Number.isNaN(e)||Number.isNaN(r))return void n.snv.badlines.push([t,"invalid maf_tumor mutant and/or total read count",i]);s.maf_tumor={f:e/r,v1:e,v2:r}}delete s.maf_tumor_v1,delete s.maf_tumor_v2}if(null!=s.maf_normal_v1&&null!=s.maf_normal_v2){if(""==s.maf_normal_v2);else{let e=Number.parseInt(s.maf_normal_v1),r=Number.parseInt(s.maf_normal_v2);if(Number.isNaN(e)||Number.isNaN(r))return void n.snv.badlines.push([t,"invalid maf_normal mutant and/or total read count",i]);s.maf_normal={f:e/r,v1:e,v2:r}}delete s.maf_normal_v1,delete s.maf_normal_v2}n.good++,"M"==s.class?n.snv.missense++:"S"==s.class&&n.snv.silent++;const c=n.geneToUpper?s.gene.toUpperCase():s.gene;n.data[c]||(n.data[c]=[]),s.dt=r.dtsnvindel,n.data[c].push(s)}},6279:(t,e,n)=>{"use strict";n.r(e),n.d(e,{duplicate:()=>a,parseheader:()=>i,parseline:()=>s});var r=n(8064),o=n(2273);function i(t,e,n){const r=t.toLowerCase().split("\t");if(r.length<=1)return"invalid file header for fusions";const o=(...t)=>{for(const e of t){const t=r.indexOf(e);if(-1!=t)return t}return-1};let i=o("gene_a","gene1","genea");return-1==i?"gene_a missing from header":(r[i]="gene1",i=o("gene_b","gene2","geneb"),-1==i?"gene_b missing from header":(r[i]="gene2",i=o("chr_a","chr1","chra"),-1==i?"chr_a missing from header":(r[i]="chr1",i=o("chr_b","chr2","chrb"),-1==i?"chr_b missing from header":(r[i]="chr2",i=o("pos_a","position_a","position1","posa"),-1==i?"pos_a missing from header":(r[i]="position1",i=o("pos_b","position_b","position2","posb"),-1==i?"pos_b missing from header":(r[i]="position2",i=o("isoform_a","refseq_a","refseq1","isoform1","sv_refseqa"),-1==i?"isoform_a missing from header":(r[i]="isoform1",i=o("isoform_b","refseq_b","refseq2","isoform2","sv_refseqb"),-1==i?"isoform_b missing from header":(r[i]="isoform2",i=o("strand_a","orta"),-1==i?"strand_a missing from header":(r[i]="strand1",i=o("strand_b","ortb"),-1==i?"strand_b missing from header":(r[i]="strand2",i=o("sample","sample_name","tumor_sample_barcode"),-1!=i&&(r[i]="sample"),i=o("patient","donor","target_case_id"),-1!=i&&(r[i]="patient"),i=o("sampletype","sample type","sample_type"),-1!=i&&(r[i]="sampletype"),i=o("disease"),-1!=i&&(r[i]="disease"),i=o("origin"),-1!=i&&(r[i]="origin"),n?(e.sv.loaded=!0,e.sv.header=r):(e.fusion.loaded=!0,e.fusion.header=r),!1))))))))))}function s(t,e,n,i){if(""==e||"#"==e[0])return;const s=e.split("\t"),a={},l=i?n.sv.header:n.fusion.header,c=i?n.sv.badlines:n.fusion.badlines;for(let t=0;t<l.length;t++)a[l[t]]=s[t];if(!a.chr1)return void c.push([t,"missing chr1",s]);if(0!=a.chr1.toLowerCase().indexOf("chr")&&(a.chr1="chr"+a.chr1),!a.chr2)return void c.push([t,"missing chr2",s]);0!=a.chr2.toLowerCase().indexOf("chr")&&(a.chr2="chr"+a.chr2);let u=a.position1;if(!u)return void c.push([t,"missing position1",s]);let f=Number.parseInt(u);if(Number.isNaN(f)||f<=0)c.push([t,"invalid value for position1",s]);else if(a.position1=f,u=a.position2,u){if(f=Number.parseInt(u),Number.isNaN(f)||f<=0)c.push([t,"invalid value for position2",s]);else if(a.position2=f,!r.parsesample(a,n,t,s,c)){if(a.isoform1&&-1!=a.isoform1.indexOf(",")){const t=a.isoform1.split(",");a.isoform1=void 0;for(const e of t)""!=e&&(a.isoform1=e)}if(a.isoform2&&-1!=a.isoform2.indexOf(",")){const t=a.isoform2.split(",");a.isoform2=void 0;for(const e of t)""!=e&&(a.isoform2=e)}if(a.gene1||(a.isoform1=void 0),a.gene2||(a.isoform2=void 0),a.gene1){n.good++;const t={dt:i?o.dtsv:o.dtfusionrna,class:i?o.mclasssv:o.mclassfusionrna,isoform:a.isoform1,mname:a.gene2||a.chr2,sample:a.sample,patient:a.patient,sampletype:a.sampletype,origin:a.origin,disease:a.disease,pairlst:[{a:{name:a.gene1,isoform:a.isoform1,strand:a.strand1,chr:a.chr1,position:a.position1},b:{name:a.gene2,isoform:a.isoform2,strand:a.strand2,chr:a.chr2,position:a.position2}}]},e=n.geneToUpper?a.gene1.toUpperCase():a.gene1;n.data[e]||(n.data[e]=[]),n.data[e].push(t)}if(a.gene2&&a.gene2!=a.gene1){n.good++;const t={dt:i?o.dtsv:o.dtfusionrna,class:i?o.mclasssv:o.mclassfusionrna,isoform:a.isoform2,mname:a.gene1||a.chr1,sample:a.sample,patient:a.patient,sampletype:a.sampletype,origin:a.origin,disease:a.disease,pairlst:[{a:{name:a.gene1,isoform:a.isoform1,strand:a.strand1,chr:a.chr1,position:a.position1},b:{name:a.gene2,isoform:a.isoform2,strand:a.strand2,chr:a.chr2,position:a.position2}}]},e=n.geneToUpper?a.gene2.toUpperCase():a.gene2;n.data[e]||(n.data[e]=[]),n.data[e].push(t)}}}else c.push([t,"missing position2",s])}function a(t){const e={};for(const n in t){if("pairlst"==n)continue;const r=t[n];"object"!=typeof r&&(e[n]=r)}if(t.pairlst){e.pairlst=[];for(const n of t.pairlst){const t={};for(const e in n)"a"!=e&&"b"!=e&&"interstitial"!=e&&(t[e]=n[e]);if(n.a){t.a={};for(const e in n.a){const r=n.a[e];"object"!=typeof r&&(t.a[e]=r)}}if(n.b){t.b={};for(const e in n.b){const r=n.b[e];"object"!=typeof r&&(t.b[e]=r)}}if(n.interstitial){t.interstitial={};for(const e in n.interstitial){const 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e={isMds:!0,noHandleOnClient:t.noHandleOnClient,label:t.label,version:t.version,annotationsampleset2matrix:t.annotationsampleset2matrix,mutationAttribute:t.mutationAttribute,locusAttribute:t.locusAttribute,alleleAttribute:t.alleleAttribute,hide_genotypedownload:t.hide_genotypedownload,hide_phewas:t.hide_phewas,sample2bam:t.sample2bam};if(t.queries&&(e.queries={}),t.track&&(e.track=K.client_copy(t)),t.singlesamplemutationjson&&(e.singlesamplemutationjson=1),t.gene2mutcount&&(e.gene2mutcount=!0,e.mutCountType=t.gene2mutcount.mutationTypes),t.assayAvailability&&(e.assayAvailability=1),t.cohort&&t.cohort.sampleAttribute){const n={};for(const e in t.cohort.sampleAttribute.attributes){const r=t.cohort.sampleAttribute.attributes[e];r.clientnoshow||(n[e]=r)}e.sampleAttribute={attributes:n}}if(t.cohort){if(t.cohort.termdb&&(e.termdb={selectCohort:t.cohort.termdb.selectCohort}),t.cohort.attributes&&t.cohort.attributes.defaulthidden&&(e.cohortHiddenAttr=t.cohort.attributes.defaulthidden),t.cohort.survivalplot){e.survivalplot={samplegroupattrlst:t.cohort.survivalplot.samplegroupattrlst,plots:[]};for(const n in t.cohort.survivalplot.plots){const r=t.cohort.survivalplot.plots[n];e.survivalplot.plots.push({key:n,name:r.name,timelabel:r.timelabel})}}if(t.cohort.mutation_signature){const n={};for(const e in t.cohort.mutation_signature.sets){const r=t.cohort.mutation_signature.sets[e];n[e]={name:r.name,signatures:r.signatures}}e.mutation_signature={sets:n}}}for(const n in t.queries){const r=t.queries[n],o={name:r.name,hideforthemoment:r.hideforthemoment};if(r.istrack){if(o.istrack=!0,o.type=r.type,o.isfull=r.isfull,null!=r.nochr&&(o.nochr=r.nochr),r.infoFilter&&(o.infoFilter=r.infoFilter),r.readcountCutoff&&(o.readcountCutoff=r.readcountCutoff),r.valueLabel&&(o.valueLabel=r.valueLabel),r.valueCutoff&&(o.valueCutoff=r.valueCutoff),r.bplengthUpperLimit&&(o.bplengthUpperLimit=r.bplengthUpperLimit),r.segmeanValueCutoff&&(o.segmeanValueCutoff=r.segmeanValueCutoff),r.lohLengthUpperLimit&&(o.lohLengthUpperLimit=r.lohLengthUpperLimit),r.type==k.tkt.mdssvcnv){if(r.groupsamplebyattr&&(o.groupsamplebyattr=r.groupsamplebyattr),o.multihidelabel_fusion=r.multihidelabel_fusion,o.multihidelabel_sv=r.multihidelabel_sv,o.multihidelabel_vcf=r.multihidelabel_vcf,o.showfullmode=r.showfullmode,o.legend_vorigin=r.legend_vorigin,o.no_loh=r.no_loh,r.expressionrank_querykey){const e=t.queries[r.expressionrank_querykey];if(o.checkexpressionrank={querykey:r.expressionrank_querykey,datatype:e.datatype},e.boxplotbysamplegroup&&e.boxplotbysamplegroup.additionals){const t=[];e.boxplotbysamplegroup.attributes&&t.push(e.boxplotbysamplegroup.attributes.map((t=>t.label)).join(", "));for(const n of e.boxplotbysamplegroup.additionals)t.push(n.label);o.checkexpressionrank.boxplotgroupers=t}}if(r.vcf_querykey){o.checkvcf={querykey:r.vcf_querykey,info:t.queries[r.vcf_querykey].info,format:{}};for(const e of t.queries[r.vcf_querykey].tracks)if(e.format)for(const t in e.format)o.checkvcf.format[t]=e.format[t]}}}else{if(!r.isgenenumeric)continue;o.isgenenumeric=!0,o.datatype=r.datatype,o.no_ase=r.no_ase}e.queries[n]=o}return e}function Ot(t){const e=t.split("\t"),n=e[4],r=e[6].split(",").filter(Boolean),o=n+"/"+r.join("/");return{chrom:e[0],chromStart:Number(e[1]),chromEnd:Number(e[2]),name:e[3],observed:o,alleles:[n,...r]}}function Et(t,e,n){if(n.query.isoform&&yt[n.query.genome].genomicNameRegexp.test(n.query.isoform))return;const[r,o]=e.makequery(n.query);if(!r)return;const i=t.newconn.prepare(r).all(o);let s;s=e.tidy?i.map((t=>e.tidy(t))):i;const a={};if(e.isgeneexpression){a.lst=s,a.isgeneexpression=!0,a.config=e.config;for(const e of t.queries)if(e.dsblocktracklst)for(const t of e.dsblocktracklst)t.type==k.tkt.junction&&(a.config.dsjunctiontk=t)}else a.lst=s;return a}function Rt(t,e){const n=[u.join(o.tpmasterdir,t.vcffile),(t.vcf.nochr?e.query.range.chr.replace("chr",""):e.query.range.chr)+":"+e.query.range.start+"-"+e.query.range.stop];return new Promise(((e,r)=>{const o=m(vt,n),i=[],s=[];o.stdout.on("data",(t=>i.push(t))),o.stderr.on("data",(t=>s.push(t))),o.on("close",(n=>{""!=s.join("").trim()&&r("error querying vcf file");const o=i.join("").trim();e({lines:""==o?[]:o.split("\n"),vcfid:t.vcf.vcfid})}))}))}function It(t){if(!t.genome)return["no genome"];const e=yt[t.genome];if(!e)return["invalid genome"];if(!e.datasets)return["genome is not equipped with datasets"];if(!t.dslabel)return["dslabel missing"];const n=e.datasets[t.dslabel];if(!n)return["invalid dslabel"];if(!n.queries)return["dataset is not equipped with queries"];if(!t.querykey)return["querykey missing"];const r=n.queries[t.querykey];return r?[null,e,n,r]:["invalid querykey"]}async function Pt(t,e,n,r,i,s){const a=await async function(t,e,n,r){const i=t.checkvcf.tracks[0],s={file:i.file,url:i.url,indexURL:i.indexURL,dir:i.dir,nochr:i.nochr,samples:i.samples,info:t.checkvcf.info,format:i.format},a=await Jt(s.file?u.join(o.tpmasterdir,s.file):s.url,(s.nochr?e.replace("chr",""):e)+":"+n+"-"+r,s.dir),l=[];for(const t of a||[]){const[e,n,r]=q.vcfparseline(t,s);for(const t of n)k.basecolor[t.ref]&&k.basecolor[t.alt]&&t.sampledata&&l.push(t)}return l}(i,e,n,r),l=[];for(const t in i.checkrnabam.samples){const n=i.checkrnabam.samples[t];n.hetsnps=[];for(const e of a){const r=Ht(e,t,i.checkrnabam);r&&r.dnacount.ishet&&n.hetsnps.push(r)}if(n.url?n.dir=await x.cache_index(n.url,n.indexURL||n.url+".bai"):n.file&&(n.file=u.join(o.tpmasterdir,n.file)),n.hetsnps.length>0){await Dt(n,n.hetsnps,e,i.checkrnabam);for(const e of n.hetsnps)e.rnacount.nocoverage||e.rnacount.ref+e.rnacount.alt<i.checkrnabam.rna_mintotalreads||l.push(t+"."+e.pos+"."+e.ref+"."+e.alt+"\t\t\t\t\t\t\t\t"+e.rnacount.ref+"\t"+e.rnacount.alt)}}l.length>0&&await async function(t,e){const n=await function(t){const e=u.join(o.cachedir,Math.random().toString());return new Promise(((n,r)=>{c.writeFile(e,t.join("\n")+"\n",(t=>{t&&r("cannot write"),n(e)}))}))}(t),r=await Gt(n);await function(t,e){return new Promise(((n,r)=>{c.readFile(t,"utf8",((t,o)=>{if(t&&r("cannot read binom pvalue"),o){for(const t of o.trim().split("\n")){const n=t.split("\t"),r=n[0].split("."),o=e[r[0]];if(!o)continue;const i=o.hetsnps.find((t=>t.pos+"."+t.ref+"."+t.alt==r[1]+"."+r[2]+"."+r[3]));i&&(i.rnacount.pvalue=Number.parseFloat(n[10]))}n()}else n()}))}))}(r,e),c.unlink(n,(()=>{})),c.unlink(r,(()=>{}))}(l,i.checkrnabam.samples),s.checkrnabam=[];for(const n in i.checkrnabam.samples){const r=i.checkrnabam.samples[n],o=[];for(const[n,s]of t){const t={gene:n,chr:e,start:s.start,stop:s.stop},a=r.hetsnps.filter((t=>t.pos>=s.start&&t.pos<=s.stop)),l=a.filter((t=>!t.rnacount.nocoverage));if(l.length>0){const e=l.reduce(((t,e)=>t+Math.abs(e.rnacount.f-.5)),0);let n=null,r=0;for(const t of l)null!=t.rnacount.pvalue&&(null==n?n=t.rnacount.pvalue:n*=t.rnacount.pvalue,t.rnacount.pvalue<=i.checkrnabam.binompvaluecutoff&&r++);null!=n&&(t.ase={markers:a.filter((t=>t.dnacount.ishet)).length,ase_markers:r,mean_delta:e/l.length,geometricmean:Math.pow(n,1/l.length)})}let c;c=r.pairedend?await Lt(r,e,s):await Ft(r,e,s),t.fpkm=1e9*c/(r.totalreads*s.exonlength),t.snps=a,o.push(t)}o.length&&s.checkrnabam.push({sample:n,genes:o})}}async function Ft(t,e,n){const r=["view","-c","-M",t.url||t.file];for(const o of n.exonunion)r.push((t.nochr?e.replace("chr",""):e)+":"+(o[0]+1)+"-"+(o[1]+1));let o;return await x.get_lines_bigfile({isbam:!0,args:r,dir:t.dir,callback:t=>o=t}),Number.parseInt(o)}function Lt(t,e,n){return new Promise(((r,o)=>{const i=["view","-M",t.url||t.file];for(const r of n.exonunion)i.push((t.nochr?e.replace("chr",""):e)+":"+(r[0]+1)+"-"+(r[1]+1));const s=m(bt,i,{cwd:t.dir}),a=m("cut",["-f1"],{cwd:t.dir}),l=m("sort",["-u"],{cwd:t.dir}),c=m("wc",["-l"],{cwd:t.dir});s.stdout.pipe(a.stdin),a.stdout.pipe(l.stdin),l.stdout.pipe(c.stdin);const u=[],f=[];c.stdout.on("data",(t=>u.push(t))),c.stderr.on("data",(t=>f.push(t))),c.on("close",(()=>{r(Number.parseInt(u.join("")))}))}))}function Dt(t,e,n,r){const o=[];for(const r of e)r.rnacount={nocoverage:1},o.push((t.nochr?n.replace("chr",""):n)+":"+(r.pos+1)+"-"+(r.pos+1));return new Promise(((n,i)=>{const s=m(_t,["mpileup","--no-reference","-a","INFO/AD","-d",999999,"-r",o.join(","),"-q",r.rnapileup_q,"-Q",r.rnapileup_Q,t.url||t.file],{cwd:t.dir});_.createInterface({input:s.stdout}).on("line",(t=>{if("#"==t[0])return;const n=Ut(t);if(!n)return;const r=e.find((t=>t.pos==n.pos));if(r){const t=n.allele2count[r.ref]||0,e=n.allele2count[r.alt]||0;t+e>0&&(r.rnacount={ref:t,alt:e,f:e/(t+e)})}})),s.on("close",(()=>{n()}))}))}function Bt(t,e,n,r,o,i){e.hideLOHwithCNVoverlap&&zt(o);const s=[];if(i){const t=new Map;for(const[e,n]of o){const r=i.sample2group.get(e);t.has(r)||t.set(r,[]),t.get(r).push({samplename:e,items:n})}if(r)for(const e of r)if(e.dt!=k.dtsnvindel)console.log("unknown dt when grouping samples from vcf: "+e.dt);else for(const n of e.sampledata){const e=i.sample2group.get(n.sampleobj.name);t.has(e)||t.set(e,[]),t.get(e).find((t=>t.samplename==n.sampleobj.name))||t.get(e).push({samplename:n.sampleobj.name,items:[]})}for(const[e,n]of t)s.push({name:e,samples:n})}else if(t.cohort&&t.cohort.annotation&&e.groupsamplebyattr){const n=new Map,i=[];for(const[r,s]of o)Zt(r,s,n,i,t,e);if(r)for(const o of r)if(o.dt!=k.dtsnvindel)console.log("unknown dt when grouping samples from vcf data: "+o.dt);else for(const r of o.sampledata)Zt(r.sampleobj.name,[],n,i,t,e);for(const t of n.values())if(s.push(t),e.groupsamplebyattr.key2group){const n=e.groupsamplebyattr.key2group.get(t.name);n&&(t.sampletotalnum=n.samples.length)}i.length&&s.push({name:"Unannotated",samples:i});for(const e of s)for(const n of e.samples)t.cohort.annotation[n.samplename]&&(n.sampletype=t.cohort.annotation[n.samplename].sample_type)}else{const t=[];for(const[e,n]of o)t.push({samplename:e,items:n});if(r)for(const e of r)if(e.dt!=k.dtsnvindel)console.log("unknown dt when grouping samples from vcf: "+e.dt);else for(const n of e.sampledata){let e=!0;for(const r of t)if(r.samplename==n.sampleobj.name){e=!1;break}e&&t.push({samplename:n.sampleobj.name,items:[]})}t.length&&s.push({samples:t})}return s}function zt(t){for(const[e,n]of t){const r=new Map,o=new Map,i=[];for(const t of n)t.dt!=k.dtloh?(t.dt==k.dtcnv&&(o.has(t.chr)||o.set(t.chr,[]),o.get(t.chr).push(t)),i.push(t)):(r.has(t.chr)||r.set(t.chr,[]),r.get(t.chr).push(t));if(0!=r.size){for(const[t,e]of r){const n=o.get(t);if(n)for(const t of e){let e=!0;for(const r of n)if(Math.max(t.start,r.start)<Math.min(t.stop,r.stop)){e=!1;break}e&&i.push(t)}else for(const t of e)i.push(t)}t.set(e,i)}}}function Zt(t,e,n,r,o,i){const s=o.cohort.annotation[t];if(!s)return void r.push({samplename:t,items:e});const a=s[i.groupsamplebyattr.attrlst[0].k];if(null==a)return void r.push({samplename:t,items:e});const l=[];for(let t=1;t<i.groupsamplebyattr.attrlst.length;t++){const e=s[i.groupsamplebyattr.attrlst[t].k];if(null==e)break;l.push(e)}l.unshift(a);const c=l.join(i.groupsamplebyattr.attrnamespacer);if(!n.has(c)){const t=[];for(const e of i.groupsamplebyattr.attrlst){const n=s[e.k];if(null==n)break;const r={k:e.k,kvalue:n};e.full&&(r.full=e.full,r.fullvalue=s[e.full]),t.push(r)}const e=[];for(const t of i.groupsamplebyattr.attrlst){const n=s[t.k];if(null==n)break;const r=(t.full?s[t.full]:null)||n;e.push(r)}n.set(c,{name:c,samples:[],attributes:t})}let u=!0;for(const r of n.get(c).samples)if(r.samplename==t){for(const t of e)r.items.push(t);u=!1;break}u&&n.get(c).samples.push({samplename:t,items:e})}function $t(t){return Number.isFinite(t.dna_mintotalreads)?Number.isFinite(t.rna_mintotalreads)?Number.isFinite(t.hetsnp_minbaf)?Number.isFinite(t.hetsnp_maxbaf)?Number.isFinite(t.rnapileup_q)?Number.isFinite(t.rnapileup_Q)?void 0:"invalid value for rnapileup_Q":"invalid value for rnapileup_q":"invalid value for hetsnp_maxbaf":"invalid value for hetsnp_minbaf":"invalid value for rna_mintotalreads":"invalid value for dna_mintotalreads"}function Gt(t){const e=t+".pvalue";return new Promise(((n,r)=>{const i=m("Rscript",[u.join(o.binpath,"utils/binom.R"),t,e]);i.on("close",(()=>{n(e)})),i.on("error",(t=>{r(`cannot do binom test: ${t}`)})),i.stderr.on("data",(t=>{r(`cannot do binom test: ${t}`)}))}))}function Ut(t){const e=t.split("\t");if(e.length<8)return;const n={pos:Number.parseInt(e[1])-1},r=[e[3],...e[4].split(",")],o={};for(const t of e[7].split(";")){const e=t.split("=");o[e[0]]=e[1]}if(o.DP&&(n.DP=Number.parseInt(o.DP)),o.AD){n.allele2count={};const t=o.AD.split(",");for(const[e,o]of r.entries())n.allele2count[o]=Number.parseInt(t[e])}return n}function Ht(t,e,n){const r=t.sampledata.find((t=>t.sampleobj.name==e));if(r){if(r.AD){const e=r.AD[t.ref]||0,o=r.AD[t.alt]||0,i={chr:t.chr,pos:t.pos,ref:t.ref,alt:t.alt,dnacount:{ref:e,alt:o}};return i.dnacount.f=o+e==0?0:o/(o+e),e+o>=n.dna_mintotalreads&&i.dnacount.f>=n.hetsnp_minbaf&&i.dnacount.f<=n.hetsnp_maxbaf&&(i.dnacount.ishet=!0),i}return null}}async function Wt(t,e,n,r,i){const s=await Jt(u.join(o.tpmasterdir,e.file),n+":"+r+"-"+i),a=new Map;if(s)for(const t of s){const e=t.split("\t"),n=JSON.parse(e[3]),r=Number.parseInt(e[1]),o=Number.parseInt(e[2]);if(a.has(n.name)){const t=a.get(n.name);t.start=Math.min(t.start,r),t.stop=Math.max(t.stop,o)}else a.set(n.name,{gene:n.name,start:r,stop:o,exonunion:[]});const i=a.get(n.name);if(n.exon)for(const t of n.exon){const e=i.exonunion.find((e=>Math.max(e[0],t[0])<Math.min(e[1],t[1])));e?(e[0]=Math.min(t[0],e[0]),e[1]=Math.max(t[1],e[1])):i.exonunion.push([t[0],t[1]])}}for(const[t,e]of a)e.exonlength=e.exonunion.reduce(((t,e)=>t+e[1]-e[0]),0);return a}async function Jt(t,e,n){return new Promise(((r,o)=>{const i=m(vt,[t,e],{cwd:n}),s=[],a=[];i.stdout.on("data",(t=>s.push(t))),i.stderr.on("data",(t=>a.push(t))),i.on("close",(()=>{const t=a.join("");t&&o(t);const e=s.join("").trim();e||r(),r(e.split("\n"))}))}))}function Vt(t,e){return new Promise(((n,r)=>{const o=m(vt,["-H",t],{cwd:e}),i=[],s=[];o.stdout.on("data",(t=>i.push(t))),o.stderr.on("data",(t=>s.push(t))),o.on("close",(()=>{const t=s.join("");t&&r(t);const e=i.join("").trim();e||r("cannot list vcf meta lines"),n(e.split("\n"))}))}))}function Yt(t,e){const n=e.findIndex((e=>e.value>=t));return-1==n||n==e.length-1?100:0==n?0:Math.ceil(100*n/e.length)}function Qt(t,e,n){if(!t.key)return[".key missing"];if(!e.cohort)return["ds.cohort missing"];if(!e.cohort.annotation)return["ds.cohort.annotation missing"];return[null,Promise.resolve().then((()=>{const r=[];for(const o in e.cohort.annotation){if(n&&!n.has(o))continue;const i=e.cohort.annotation[o][t.key];null!=i&&r.push({sample:o,value:i})}return{id:t.id,items:r}}))]}function Kt(t,e,n,i){if(!t.genename)return["genename missing"];const s=t.genename.toLowerCase();if(!t.chr)return["chr missing"];if(!Number.isInteger(t.start)||!Number.isInteger(t.stop))return["invalid start/stop coordinate"];if(t.stop-t.start>1e7)return["gene feature too long (> 10Mb)"];return[null,Promise.resolve().then((()=>{if(!n.file)return x.cache_index(n.url,n.indexURL)})).then((e=>new Promise(((a,l)=>{const c=[],f=m(vt,[n.file?u.join(o.tpmasterdir,n.file):n.url,t.chr+":"+t.start+"-"+t.stop],{cwd:e});_.createInterface({input:f.stdout}).on("line",(t=>{const e=t.split("\t"),n=JSON.parse(e[3]);n.gene&&n.gene.toLowerCase()==s&&n.sample&&(i&&!i.has(n.sample)||c.push(n))}));const d=[];f.stderr.on("data",(t=>d.push(t))),f.on("close",(e=>{const n=d.join("");!n||r(n)?a({id:t.id,items:c}):l(n)}))}))))]}function Xt(t,e,n,i){if(!t.chr)return["chr missing"];if(!Number.isInteger(t.start)||!Number.isInteger(t.stop))return["invalid start/stop coordinate"];if(t.stop-t.start>1e7)return["look range too big 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x.query_bigbed_by_coord(r.snp.bigbedfile,t.query.chr,e.start,e.stop);for(const e of n){const n=Ot(e);if(t.query.alleleLst){let e=!1;for(const r of t.query.alleleLst)if(r&&!n.alleles.includes(r)){e=!0;break}if(e)continue}o.push(n)}}}else{if(!t.query.byName)throw"unknown query method";if(!Array.isArray(t.query.lst))throw".lst[] missing";for(const e of t.query.lst){if(r.genomicNameRegexp.test(e))continue;const t=await x.query_bigbed_by_name(r.snp.bigbedfile,e);for(const e of t){const t=Ot(e);o.push(t)}}}e.send({results:o})}catch(t){return t.stack&&console.log(t.stack),e.send({error:t.message||t})}})),Nt.get(St+"/clinvarVCF",(async function(t,e){Mt(t);try{const n=yt[t.query.genome];if(!n)throw"unknown genome";if(!n.clinvarVCF)throw"no clinvar for this genome";const r=Number(t.query.pos);if(!Number.isInteger(r))throw"pos is not integer";if(r<0)throw"pos is not positive integer";if(!t.query.chr)throw"chr missing";{const e=n.chrlookup[t.query.chr.toUpperCase()];if(!e)throw"invalid 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n.send({error:r});a.checkrnabam=t.query.checkrnabam}}else{if(i=yt[t.query.genome],!i)return n.send({error:"invalid genome"});if(!i.datasets)return n.send({error:"genome is not equipped with datasets"});if(s=i.datasets[t.query.dslabel],!s)return n.send({error:"invalid dslabel"});if(t.query.getsample4disco)return function(t,e,n,r){if(t.query.iscustom)return e.send({error:"not for custom track"});if(!r.singlesamplemutationjson)return e.send({error:"singlesamplemutationjson not available for this dataset"});const i=t.query.getsample4disco,s=r.singlesamplemutationjson.samples[i];if(!s)return e.send({error:"no data"});const a=u.join(o.tpmasterdir,s);c.readFile(a,{encoding:"utf8"},((t,n)=>{if(t)return e.send({error:"error getting data for this sample"});e.send({text:n})}))}(t,n,0,s);if(t.query.gettrack4singlesample)return function(t,e,n){const r=t.query.gettrack4singlesample;if(t.query.iscustom)return e.send({error:"no server-side config available for custom track"});if(!n.sampleAssayTrack)return e.send({});return e.send({tracks:n.sampleAssayTrack.samples.get(r)})}(t,n,s);if(t.query.findsamplename)return function(t,e,n){if(t.query.iscustom)return e.send({error:"cannot search sample by name in custom track"});const r=t.query.findsamplename.toLowerCase(),o=[];if(!n.cohort.__samplelst){n.cohort.__samplelst=[];for(const t in n.cohort.annotation)n.cohort.__samplelst.push({name:t,low:t.toLowerCase()})}i(n.cohort.__samplelst);for(const t in n.queries){const e=n.queries[t];if(e.type==k.tkt.mdssvcnv&&e.groupsamplebyattr)for(const t of o){const r=n.cohort.annotation[t.name];if(!r)continue;const o=[];for(const t of e.groupsamplebyattr.attrlst){const e=r[t.k];e&&o.push({k:t.k,kvalue:e})}o.length&&(t.attributes=o,t.grouplabel=o.map((t=>t.kvalue)).join(e.groupsamplebyattr.attrnamespacer))}}if(n.cohort&&n.cohort.sampleAttribute&&n.cohort.sampleAttribute.attributes&&n.cohort.annotation)for(const t of o){const e=n.cohort.annotation[t.name];if(!e)continue;const r=[];for(const t in n.cohort.sampleAttribute.attributes){if(n.cohort.sampleAttribute.attributes[t].clientnoshow)continue;const o=e[t];null!=o&&r.push({k:t,v:o})}r.length&&(t.attr=r)}if(n.sampleAssayTrack)for(const t of o){const e=n.sampleAssayTrack.samples.get(t.name);e&&(t.num_assay_tracks=e.length)}if(n.cohort&&n.cohort.mutation_signature)for(const t in n.cohort.mutation_signature.sets){const e=n.cohort.mutation_signature.sets[t];if(e.samples)for(const t of o)e.samples.map.has(t.name)&&(t.mutation_signature=1)}if(n.singlesamplemutationjson)for(const t of o)n.singlesamplemutationjson.samples[t.name]&&(t.disco=1);return e.send({result:o});function i(t){for(const e of t){if(o.length>10)return;-1!=e.low.indexOf(r)&&(o.find((t=>t.name==e.name))||o.push(e))}}}(t,n,s);if(t.query.assaymap)return async function(t,e,n){try{if(!n.assayAvailability)throw"assay availability not enabled for this dataset";const r=new 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expression rank";if(!t.query.sample)throw"sample missing";if(t.query.iscustom){if(n=yt[t.query.genome],!n)throw"invalid genome";if(!t.query.file&&!t.query.url)throw"no file or url for expression data";i={},s={file:t.query.file,url:t.query.url,indexURL:t.query.indexURL}}else{const[e,r,o,a]=It(t.query);if(e)throw e;if(n=r,i=o,s=a,!s.samples)throw"total samples missing from server config";if(-1==s.samples.indexOf(t.query.sample))throw{nodata:1}}if(s.viewrangeupperlimit&&t.query.rglst.reduce(((t,e)=>t+e.stop-e.start),0)>s.viewrangeupperlimit)throw"zoom in under "+k.bplen(s.viewrangeupperlimit)+" to view data";if(t.query.levelkey){if(!t.query.levelvalue)throw"levelvalue is required when levelkey is used";if(!i.cohort||!i.cohort.annotation)throw".cohort.annotation missing from dataset"}if(!s.file){if(!s.url)throw"file or url missing";return x.cache_index(s.url,s.indexURL)}})).then((e=>{const n=[];for(const l of t.query.rglst)n.push(new Promise(((n,c)=>{const f=m(vt,[s.file?u.join(o.tpmasterdir,s.file):s.url,l.chr+":"+l.start+"-"+l.stop],{cwd:e}),d=_.createInterface({input:f.stdout}),h=new Map;d.on("line",(e=>{const n=e.split("\t"),r=JSON.parse(n[3]);if(!r.gene)return;if(!r.sample)return;if(!Number.isFinite(r.value))return;const o=n[0],s=Number.parseInt(n[1]),l=Number.parseInt(n[2]);if(r.sample==t.query.sample)return h.has(r.gene)||h.set(r.gene,{chr:o,start:s,stop:l,allvalues:[]}),h.get(r.gene).thisvalue=r.value,void(r.ase&&(h.get(r.gene).ase=r.ase));if(t.query.attributes){const e=i.cohort.annotation[r.sample];if(!e)return;for(const n of t.query.attributes)if(n.k&&n.kvalue&&n.kvalue!=e[n.k])return}a.add(r.sample),h.has(r.gene)||h.set(r.gene,{chr:o,start:s,stop:l,allvalues:[]}),h.get(r.gene).allvalues.push({value:r.value})}));const p=[];f.stderr.on("data",(t=>p.push(t))),f.on("close",(t=>{const e=p.join("");e&&!r(e)&&c({message:e}),n(h)}))})));return Promise.all(n)})).then((t=>{const n=[];for(const e of t)for(const[t,r]of e)null!=r.thisvalue&&(r.allvalues.sort(((t,e)=>t.value-e.value)),r.rank=Yt(r.thisvalue,r.allvalues),delete r.allvalues,r.gene=t,n.push(r));e.send({result:n,samplecount:a.size})})).catch((t=>{t.stack&&console.log(t),t.nodata?e.send({nodata:1}):e.send({error:t.message?t.message:t})}))})),Nt.post(St+"/mdsgeneboxplot",st(yt)),Nt.post(St+"/mdsgenevalueonesample",(async function(t,e){const n=t.query;try{if(!n.sample)throw".sample missing";if(!n.genes)throw".genes[] missing";let r,i,s;if(t.query.iscustom){if(r=yt[n.genome],!r)throw"invalid genome";if(!n.file&&!n.url)throw"no file or url for expression data";i={},s={file:n.file,url:n.url,indexURL:n.indexURL}}else{const[t,e,o,a]=It(n);if(t)throw t;r=e,i=o,s=a}const a=s.file?null:await x.cache_index(s.url,s.indexURL),l={};let c=!0;for(const t of n.genes){let e;await x.get_lines_bigfile({args:[s.file?u.join(o.tpmasterdir,s.file):s.url,t.chr+":"+t.start+"-"+t.stop],dir:a,callback:r=>{const o=r.split("\t");if(!o[3])return;const i=JSON.parse(o[3]);i.gene==t.gene&&i.sample==n.sample&&(e=i.value)}}),Number.isFinite(e)&&(l[t.gene]=e,c=!1)}c?e.send({nodata:1}):e.send({result:l})}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message||t})}})),Nt.post(St+"/vcf",(async function(t,e){try{const[n,r,o]=ue(t);if(n)throw n;const i=o?await x.cache_index(r,t.query.indexURL):null;if(!t.query.rglst)throw"rglst missing";const s=[];for(const e of t.query.rglst)await x.get_lines_bigfile({args:[r,e.chr+":"+e.start+"-"+e.stop],dir:i,callback:t=>s.push(t)});e.send({linestr:s.join("\n")})}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message||t})}})),Nt.get(St+"/vcfheader",(async function(t,e){try{if(!t.query.genome)throw"genome missing";const n=yt[t.query.genome];if(!n)throw"invalid genome";const[r,o,i]=ue(t);if(r)throw r;const s=i?await x.cache_index(o,t.query.indexURL):null;e.send({metastr:(await x.get_header_tabix(o,s)).join("\n"),nochr:await x.tabix_is_nochr(o,s,n)})}catch(t){t.stack&&console.error(t.stack),e.send({error:t.message||t})}})),Nt.post(St+"/translategm",(async function(t,e){try{const n=yt[t.query.genome];if(!n)throw"invalid genome";const r=t.query.gm;if(!r)throw"missing gm{}";if(!r.chr)throw"gm.chr missing";if(!r.start)throw"gm.start missing";if(!Number.isInteger(r.start))throw"gm.start not integer";if(!r.stop)throw"gm.stop missing";if(!Number.isInteger(r.stop))throw"gm.stop not integer";const o=await x.get_fasta(n,r.chr+":"+(r.start+1)+"-"+r.stop),i=k.fasta2gmframecheck(r,o);e.send({frame:i})}catch(t){e.send({error:t.message||t}),t.stack&&console.log(t.stack)}})),Nt.get(St+"/hicstat",(async function(t,e){Mt(t);try{const[n,r,o]=ue(t);if(n)throw"illegal file name";o||await x.file_is_readable(r);const i=await it(r,o);e.send({out:i})}catch(t){e.send({error:t.message||t}),t.stack&&console.log(t.stack)}})),Nt.post(St+"/hicdata",(function(t,e){const[n,r,o]=ue(t);if(n)return void e.send({error:"illegal file name"});const i=[t.query.nmeth||"NONE",r,t.query.pos1,t.query.pos2,t.query.isfrag?"FRAG":"BP",t.query.resolution],s=m(wt,i),a=_.createInterface({input:s.stdout}),l=[],c=[];let u=0,f=0;a.on("line",(e=>{const n=e.split("\t");if(3!=n.length)return void u++;const r=Number.parseInt(n[0]),o=Number.parseInt(n[1]),i=Number.parseFloat(n[2]);Number.isNaN(r)||Number.isNaN(o)||Number.isNaN(i)?f++:null!=t.query.mincutoff&&i<=t.query.mincutoff||l.push([r,o,i])})),s.stderr.on("data",(t=>c.push(t))),s.on("close",(()=>{const t=c.join("");return t?e.send({error:t}):u?e.send({error:u+" lines have other than 3 fields"}):f?e.send({error:f+" lines have non-numerical values in any of the 3 fields"}):void e.send({items:l})}))})),Nt.post(St+"/samplematrix",(function(t,e){Promise.resolve().then((()=>{const e=yt[t.query.genome];if(!e)throw"invalid genome";let n,r;if(t.query.iscustom){if(!t.query.querykey2tracks)throw"querykey2tracks{} missing for custom dataset";n={queries:{}};for(const e in t.query.querykey2tracks){const r=t.query.querykey2tracks[e];if(!r.type)throw'missing "type" for a data track';if(r.type==k.tkt.mdsvcf){const r=t.query.querykey2tracks[e];r.type=k.mdsvcftype.vcf,n.queries[e]={type:k.tkt.mdsvcf,info:r.info,tracks:[r]}}else if(r.type==k.tkt.mdssvcnv)n.queries[e]=r;else{if(r.type!=k.tkt.mdsexpressionrank)throw"unknown type of data track: "+r.type;n.queries[e]=r}}}else{if(!e.datasets)throw"genome is not equipped with datasets";if(!t.query.dslabel)throw"dslabel missing";if(n=e.datasets[t.query.dslabel],!n)throw"invalid dslabel";if(!n.queries)throw"dataset is not equipped with queries"}if(t.query.sampleset)r=new Set(t.query.sampleset);else if(t.query.limitsamplebyeitherannotation){if(!n.cohort)throw"limitsamplebyeitherannotation but no cohort in ds";if(!n.cohort.annotation)throw"limitsamplebyeitherannotation but no cohort.annotation in ds";r=new Set;for(const e in n.cohort.annotation){const o=n.cohort.annotation[e];for(const n of t.query.limitsamplebyeitherannotation)if(o[n.key]==n.value){r.add(e);break}}}const o=[];for(const e of t.query.features){let t,i=[];if(e.querykey){if(!n.queries)throw"using querykey for a feature but no ds.queries";if(t=n.queries[e.querykey],!t)throw"unknown dsquery by key "+e.querykey}else if(e.querykeylst){if(!n.queries)throw"using querykeylst for a feature but no ds.queries";for(const t of e.querykeylst){const e=n.queries[t];if(!e)throw'unknown key "'+t+'" from querykeylst';i.push(e)}if(0==i.length)throw"no valid keys in querykeylst"}else if(!e.issampleattribute)throw"unknown way to query a feature";if(e.isgenevalue){const[i,s]=Kt(e,n,t,r);if(i)throw"error with isgenevalue: "+i;o.push(s)}else if(e.iscnv){const[i,s]=Xt(e,n,t,r);if(i)throw"error with iscnv: "+i;o.push(s)}else if(e.isloh){const[i,s]=te(e,n,t,r);if(i)throw"error with isloh: "+i;o.push(s)}else if(e.isvcf){const[i,s]=ie(e,n,t,r);if(i)throw"error with isvcf: "+i;o.push(s)}else if(e.isitd){const[i,s]=ee(e,n,t,r);if(i)throw"error with isitd: "+i;o.push(s)}else if(e.issvfusion){const[i,s]=ne(e,n,t,r);if(i)throw"error with issvfusion: "+i;o.push(s)}else if(e.issvcnv){const[i,s]=re(e,n,t,r);if(i)throw"error with issvcnv: "+i;o.push(s)}else if(e.ismutation){const[t,s]=oe(e,n,i,r);if(t)throw"error with ismutation: "+t;o.push(s)}else{if(!e.issampleattribute)throw"unknown type of feature";{const[t,i]=Qt(e,n,r);if(t)throw"error with issampleattribute: "+t;o.push(i)}}}return Promise.all(o)})).then((t=>{e.send({results:t})})).catch((t=>{e.send({error:"string"==typeof t?t:t.message}),t.stack&&console.error(t.stack)}))})),Nt.get(St+"/mdssamplescatterplot",(async function(t,e){Mt(t);try{const n=yt[t.query.genome];if(!n)throw"invalid genome";const r=n.datasets[t.query.dslabel];if(!r)throw"invalid dataset";if(!r.cohort)throw"no cohort for dataset";if(!r.cohort.annotation)throw"cohort.annotation missing for dataset";const o=r.cohort.scatterplot;if(!o)throw"scatterplot not supported for this dataset";const i=[];for(const e in r.cohort.annotation){const n=r.cohort.annotation[e];if(t.query.subsetkey&&n[t.query.subsetkey]!=t.query.subsetvalue)continue;const s=n[o.x.attribute];if(!Number.isFinite(s))continue;const a=n[o.y.attribute];Number.isFinite(a)&&i.push({sample:e,x:s,y:a,s:n})}e.send({colorbyattributes:o.colorbyattributes,colorbygeneexpression:o.colorbygeneexpression,querykey:o.querykey,dots:i,tracks:o.tracks})}catch(t){t.stack&&console.error(t.stack),e.send({error:t.message||t})}})),Nt.post(St+"/mdssamplesignature",(function(t,e){try{const n=t.query;if(!n.sample)throw".sample missing";const r=yt[n.genome];if(!r)throw"invalid genome";const o=r.datasets[n.dslabel];if(!o)throw"invalid dataset";if(!o.cohort)throw"no cohort for dataset";if(!o.cohort.mutation_signature)throw"no mutation_signature for cohort";const i=[];for(const t in o.cohort.mutation_signature.sets){const e=o.cohort.mutation_signature.sets[t];if(!e.samples)continue;const r=e.samples.map.get(n.sample);if(!r)continue;const s=[];for(const t in e.signatures)r[t]&&s.push({k:t,v:r[t]});s.length&&i.push({key:t,valuename:e.samples.valuename,annotation:s.sort(((t,e)=>e.v-t.v))})}e.send({lst:i})}catch(t){t.stack&&console.error(t.stack),e.send({error:t.message||t})}})),Nt.post(St+"/mdssurvivalplot",lt(yt)),Nt.post(St+"/fimo",rt.handle_closure(yt)),Nt.all(St+"/termdb",P.handle_request_closure(yt)),Nt.all(St+"/termdb-barsql",D.handle_request_closure(yt)),Nt.post(St+"/singlecell",nt.handle_singlecell_closure(yt)),Nt.post(St+"/massSession",et.save),Nt.get(St+"/massSession",et.get),Nt.get(St+"/isoformbycoord",(async function(t,e){try{const n=yt[t.query.genome];if(!n)throw"invalid genome";if(!t.query.chr)throw"chr missing";const r=Number(t.query.pos);if(!Number.isInteger(r))throw"pos must be positive integer";const i=n.tracks.find((t=>t.__isgene));i||reject("no gene track");const s=[];await x.get_lines_bigfile({args:[u.join(o.tpmasterdir,i.file),t.query.chr+":"+r+"-"+r],callback:t=>{const e=t.split("\t")[3];if(!e)return;const r=JSON.parse(e);if(!r.isoform)return;const o={isoform:r.isoform},i=n.genedb.getjsonbyisoform.get(r.isoform);i&&(o.name=JSON.parse(i.genemodel).name,o.isdefault=i.isdefault),s.push(o)}}),e.send({lst:s})}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message||t})}})),Nt.post(St+"/ase",(async function(t,e){const n=t.query,r=3e6,i=5e5;try{const t=yt[n.genome];if(!t)throw"invalid genome";if(!n.samplename)throw"samplename missing";if(!n.chr)throw"no chr";if(!n.start||!n.stop)throw"no start/stop";if(!n.rnabarheight)throw"no rnabarheight";if(!n.dnabarheight)throw"no dnabarheight";if(!Number.isInteger(n.barypad))throw"invalid barypad";if(n.rnamax&&!Number.isFinite(n.rnamax))throw"invalid value for rnamax";if(!n.checkrnabam)throw".checkrnabam{} missing";const s=$t(n.checkrnabam);if(s)throw s;if(n.refcolor||(n.refcolor="blue"),n.altcolor||(n.altcolor="red"),!t.tracks)throw"genome.tracks[] missing";const a=t.tracks.find((t=>t.__isgene));if(!a)throw"no gene track from this genome";await async function(t,e){if(t.rnabamfile)t.rnabamfile=u.join(o.tpmasterdir,t.rnabamfile);else{if(!t.rnabamurl)throw"no file or url for rna bam";t.rnabamurl_dir=await x.cache_index(t.rnabamurl,t.rnabamindexURL||t.rnabamurl+".bai")}if(t.rnabam_nochr=await x.bam_ifnochr(t.rnabamfile||t.rnabamurl,e,t.rnabamurl_dir),t.vcffile)t.vcffile=u.join(o.tpmasterdir,t.vcffile);else{if(!t.vcfurl)throw"no file or url for vcf";t.vcfurl_dir=await x.cache_index(t.vcfurl,t.vcfindexURL)}t.vcf_nochr=await x.tabix_is_nochr(t.vcffile||t.vcfurl,t.vcfurl_dir,e)}(n,t);const l=await Wt(t,a,n.chr,n.start,n.stop),f={};if(n.stop-n.start<r)for(const[t,e]of l){const t={file:n.rnabamfile,url:n.rnabamurl,dir:n.rnabamurl_dir,nochr:n.rnabam_nochr};let r;r=n.rnabamispairedend?await Lt(t,n.chr,e):await Ft(t,n.chr,e),e.fpkm=1e9*r/(n.rnabamtotalreads*e.exonlength)}else f.fpkmrangelimit=r;const[d,h,p,y]=function(t,e){let n=t.start,r=t.stop;for(const[t,o]of e)n=Math.min(n,o.start),r=Math.max(r,o.stop);const o=t.start,i=t.stop;return[n,r,o,i]}(n,l),v=await async function(t,e,n,r,o){const i=await Vt(t.vcffile||t.vcfurl,t.vcfurl_dir),[s,a,l,c]=q.vcfparsemeta(i);if(c)throw c;const u={info:s,format:a,samples:l},f=await Jt(t.vcffile||t.vcfurl,(t.vcf_nochr?t.chr.replace("chr",""):t.chr)+":"+r+"-"+o,t.vcfurl_dir),d=[];for(const e of f||[]){const[n,r,o]=q.vcfparseline(e,u);for(const e of r){if(!k.basecolor[e.ref]||!k.basecolor[e.alt])continue;if(!e.sampledata)continue;const n=Ht(e,t.samplename,t.checkrnabam);n&&d.push(n)}}const h=[];for(const t of d)for(const[e,r]of n)if(t.pos>=r.start&&t.pos<=r.stop){h.push(t);break}return h}(n,0,l,d,h);for(const t of v)t.rnacount={nocoverage:1};let b,w;y-p>=i?f.covplotrangelimit=i:(n.rnamax?b=n.rnamax:(b=await async function(t,e,n){let r=0;return await x.get_lines_bigfile({isbam:!0,args:["depth","-r",(t.rnabam_nochr?t.chr.replace("chr",""):t.chr)+":"+(e+1)+"-"+(n+1),"-g","DUP",t.rnabamurl||t.rnabamfile],dir:t.rnabamurl_dir,callback:t=>{const e=t.split("\t");if(3!=e.length)return;const n=Number.parseInt(e[2]);Number.isInteger(n)&&(r=Math.max(r,n))}}),r}(n,p,y),f.rnamax=b),w=await async function(t,e,n,r,o){const i=new Map;for(const t of r)t.dnacount.ishet&&t.pos>=e&&t.pos<=n&&i.set(t.pos,t);const s=g(t.width*t.devicePixelRatio,(t.rnabarheight+t.barypad+t.dnabarheight)*t.devicePixelRatio),a=s.getContext("2d");t.devicePixelRatio>1&&a.scale(t.devicePixelRatio,t.devicePixelRatio);let l,c,u=!1;n-e<=t.width?(u=!0,l=1,c=t.width/(n-e),a.lineWidth=c):(c=1,l=(n-e)/t.width);return await x.get_lines_bigfile({isbam:!0,args:["depth","-r",(t.rnabam_nochr?t.chr.replace("chr",""):t.chr)+":"+(e+1)+"-"+(n+1),"-g","DUP",t.rnabamurl||t.rnabamfile],dir:t.rnabamurl_dir,callback:n=>{const r=n.split("\t");if(3!=r.length)return;const 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Promise(((t,r)=>{c.writeFile(e,n.join("\n")+"\n",(n=>{n&&r("cannot write"),t(e)}))}))}(n),i=await Gt(r);await function(t,e){return new Promise(((n,r)=>{c.readFile(e,"utf8",((e,o)=>{e&&r("cannot read binom pvalue"),o||n();for(const e of o.trim().split("\n")){const n=e.split("\t"),r=t.find((t=>n[0]==t.pos+"."+t.ref+"."+t.alt));r&&(r.rnacount.pvalue=Number.parseFloat(n[10]))}n()}))}))}(t,i),c.unlink(r,(()=>{})),c.unlink(i,(()=>{}))}(v,n),f.genes=function(t,e,n){const r=[];for(const[o,i]of e){r.push(i);const e=t.filter((t=>t.pos>=i.start&&t.pos<=i.stop));if(0==e.length){i.nosnp=1;continue}i.snps=e;const o=e.filter((t=>null!=t.rnacount.pvalue));if(0==o.length){i.nornasnp=1;continue}const s=o.reduce(((t,e)=>t+Math.abs(e.rnacount.f-.5)),0);let a=null,l=0;for(const t of 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genome";if(!n.genedb.get_gene2canonicalisoform)throw"gene2canonicalisoform not supported on this genome";const r=n.genedb.get_gene2canonicalisoform.get(t.query.gene);e.send(r)}catch(t){e.send({error:t.message||t}),t.stack&&console.log(t.stack)}})),Nt.get(St+"/ideogram",(function(t,e){try{const n=yt[t.query.genome];if(!n)throw"invalid genome";if(!n.genedb.hasIdeogram)throw"ideogram not supported on this genome";if(!t.query.chr)throw".chr missing";const r=n.genedb.getIdeogramByChr.all(t.query.chr);if(!r.length)throw"no ideogram data for this chr";e.send(r)}catch(t){e.send({error:t.message||t})}})),async function(){try{await c.promises.stat(o.tpmasterdir)}catch(t){const e="Error with "+o.tpmasterdir+": "+t.code;if("validate"==process.argv[2])throw e;return void console.log("\n!!! "+e+"\n")}if(function(){if(o.features.skip_checkDependenciesAndVersions)return void console.log("SKIPPED checkDependenciesAndVersions()");const t=["jsonlite","cmprsk","hwde","lmtest"];for(const e of t){const t=p.spawnSync(o.Rscript,["-e",`suppressPackageStartupMessages(library("${e}"))`],{encoding:"utf8"});if(t.stderr.trim())throw t.stderr}{const t=p.execSync(o.samtools+" --version",{encoding:"utf8"}).trim().split("\n"),[e,n]=t[0].split(" ");if("samtools"!=e||!n)throw'cannot run "samtools version"';const[r,i]=n.split(".");if("1"!=r)throw"samtools not 1.*";if(Number(i)<10)throw"samtools not >= 1.10"}{const t=p.execSync(o.bcftools+" -v",{encoding:"utf8"}).trim().split("\n"),[e,n]=t[0].split(" ");if("bcftools"!=e||!n)throw'cannot run "bcftools version"';const[r,i]=n.split(".");if("1"!=r)throw"bcftools not 1.*";if(Number(i)<10)throw"bcftools not >= 1.10"}}(),xt=function(){const t=c.statSync(o.binpath+"/server.js").mtime,e=c.existsSync("public/bin/proteinpaint.js")&&c.statSync("public/bin/proteinpaint.js").mtime||0;return t>e?t:e}(),kt=Date(Date.now()).toString().split(" ").slice(0,5).join(" "),null!=o.base_zindex){const t=Number.parseInt(o.base_zindex);if(Number.isNaN(t)||t<=0)throw"base_zindex must be positive integer";o.base_zindex=t}if(o.jwt){if(!o.jwt.secret)throw"jwt.secret missing";if(!o.jwt.permissioncheck)throw"jwt.permissioncheck missing"}if(!o.tpmasterdir)throw".tpmasterdir missing";if(!o.cachedir)throw".cachedir missing";o.cachedir_massSession=await pe("massSession"),o.cachedir_massSessionTrash=await pe("massSessionTrash"),o.cache_snpgt={dir:await pe("snpgt"),fileNameRegexp:/[^\w]/,sampleColumn:6},o.cachedir_bam=await pe("bam"),o.cachedir_genome=await pe("genome"),o.cachedir_ssid=await pe("ssid"),o.commonOverrides&&k.applyOverrides(o.commonOverrides);if(!o.genomes)throw".genomes[] missing";if(!Array.isArray(o.genomes))throw".genomes[] not array";for(const t of o.genomes){if(!t.name)throw".name missing from a genome: "+JSON.stringify(t);if(!t.file)throw".file missing from genome "+t.name;const e=u.join(process.cwd(),t.file),n=require(c.existsSync(e)?e:t.file),r=n.default||n;if(yt[t.name]=r,!r.genomefile)throw".genomefile missing from .js file of genome "+t.name;if("NA"==r.genomefile||(r.genomefile=u.join(o.tpmasterdir,r.genomefile)),r.genomicNameRegexp||(r.genomicNameRegexp=/[^a-zA-Z0-9.:_-]/),r.tracks||(r.tracks=[]),t.tracks)for(const e of t.tracks)r.tracks.push(e);if(t.datasets&&(r.rawdslst=t.datasets),t.snp&&(r.snp=t.snp),t.blat){if(!t.blat.host)throw".blat.host missing for "+t.name;if(!t.blat.port)throw".blat.port missing for "+t.name;r.blat=t.blat}if(t.nosnp&&delete r.snp,t.nohicenzyme&&delete r.hicenzymefragment,t.nohicdomain&&delete r.hicdomain,r.genedb&&t.no_gene2canonicalisoform&&delete r.genedb.gene2canonicalisoform,t.updateAttr)for(const e of t.updateAttr){let t=r;for(const[n,r]of e.entries())if(t)if("object"==typeof r)for(const e in r)t[e]=r[e];else{if("string"==typeof t[r]){e[n+1]&&(t[r]=e[n+1]);break}t=t[r]}}}o.defaultgenome&&yt[o.defaultgenome]&&(yt[o.defaultgenome].isdefault=!0);for(const t in yt){const n=yt[t];if(!n.majorchr)throw t+": majorchr missing";if(!n.defaultcoord)throw t+": defaultcoord missing";if(await x.get_fasta(n,n.defaultcoord.chr+":"+n.defaultcoord.start+"-"+(n.defaultcoord.start+1)),n.tracks||(n.tracks=[]),"string"==typeof n.majorchr){const e=n.majorchr.trim().split(/[\s\t\n]+/),r={},o=[];for(let n=0;n<e.length;n+=2){const i=e[n],s=Number.parseInt(e[n+1]);if(Number.isNaN(s))throw t+" majorchr invalid chr size for "+i+" ("+e[n+1]+")";r[i]=s,o.push(i)}n.majorchr=r,n.majorchrorder=o}n.chrlookup={};for(const t in n.majorchr)n.chrlookup[t.toUpperCase()]={name:t,len:n.majorchr[t],major:!0};if(n.minorchr){if("string"==typeof n.minorchr){const e=n.minorchr.trim().split(/[\s\t\n]+/),r={};for(let n=0;n<e.length;n+=2){const o=Number.parseInt(e[n+1]);if(Number.isNaN(o))throw t+" minorchr invalid chr size for "+e[n]+" ("+e[n+1]+")";r[e[n]]=o}n.minorchr=r}for(const t in n.minorchr)n.chrlookup[t.toUpperCase()]={name:t,len:n.minorchr[t]}}if(n.genedb){if(!n.genedb.dbfile)throw t+": .genedb.dbfile missing";try{console.log("Connecting",n.genedb.dbfile),n.genedb.db=x.connect_db(n.genedb.dbfile)}catch(t){throw`Cannot connect genedb: ${n.genedb.dbfile}: ${t}`}n.genedb.getnamebynameorisoform=n.genedb.db.prepare("select name from genes where name=? or isoform=?"),n.genedb.getnamebyisoform=n.genedb.db.prepare("select distinct name from genes where isoform=?"),n.genedb.getjsonbyname=n.genedb.db.prepare("select isdefault,genemodel from genes where name=?"),n.genedb.getjsonbyisoform=n.genedb.db.prepare("select isdefault,genemodel from genes where isoform=?"),n.genedb.getnameslike=n.genedb.db.prepare("select distinct name from genes where name like ? limit 20");const e=ht(n.genedb.db);e.has("genealias")&&(n.genedb.getNameByAlias=n.genedb.db.prepare("select name from genealias where alias=?"),n.genedb.tableSize=n.genedb.db.prepare("select count(*) from genealias where alias=?")),e.has("gene2coord")&&(n.genedb.getCoordByGene=n.genedb.db.prepare("select * from gene2coord where name=?")),e.has("ideogram")?(n.genedb.hasIdeogram=!0,n.genedb.getIdeogramByChr=n.genedb.db.prepare("select * from ideogram where chromosome=?")):n.genedb.hasIdeogram=!1,e.has("gene2canonicalisoform")&&(n.genedb.get_gene2canonicalisoform=n.genedb.db.prepare("select isoform from gene2canonicalisoform where gene=?")),e.has("buildDate")&&(n.genedb.get_buildDate=n.genedb.db.prepare("select date from buildDate")),n.genedb.hasTable_refseq2ensembl=e.has("refseq2ensembl"),n.genedb.sqlTables=[...e],n.genedb.tableSize={};for(const t of e)"buildDate"!=t&&(n.genedb.tableSize[t]=n.genedb.db.prepare(`select count(*) as size from ${t}`).get().size)}if(n.termdbs)for(const r in n.termdbs)dt(n.termdbs[r],e.features),console.log(`${r} initiated as ${t}-level termdb`);for(const t of n.tracks)if(t.__isgene){if(!t.file)throw"Tabix file missing for gene track: "+JSON.stringify(t);try{await x.validate_tabixfile(u.join(o.tpmasterdir,t.file))}catch(e){throw"Error with "+t.file+": "+e}}if(n.proteindomain){if(!n.proteindomain.dbfile)throw t+".proteindomain: missing dbfile for sqlite db";if(!n.proteindomain.statement)throw t+".proteindomain: missing statement for sqlite db";let e;try{console.log("Connecting",n.proteindomain.dbfile),e=x.connect_db(n.proteindomain.dbfile)}catch(t){throw"Error with "+n.proteindomain.dbfile+": "+t}n.proteindomain.getbyisoform=e.prepare(n.proteindomain.statement)}if(n.snp){if(!n.snp.bigbedfile)throw t+".snp: missing bigBed file";n.snp.bigbedfile=u.join(o.tpmasterdir,n.snp.bigbedfile),await x.file_is_readable(n.snp.bigbedfile)}if(n.clinvarVCF){if(!n.clinvarVCF.file)throw t+".clinvarVCF: VCF file 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le=Object.freeze([".bam",".bai",".gz",".tbi",".csi",".bw",".bb"]);function ce(t,e=!1,n=!0){if("/"==t[0])return!0;if(t.includes('"')||t.includes("'"))return!0;if(t.includes("|")||t.includes("&"))return!0;if(t.includes(" "))return!0;if(-1!=t.indexOf(".."))return!0;if(t.match(/(\<script|script\>)/i))return!0;if(e&&o.whiteListPaths){let e=!0;for(const n of o.whiteListPaths){if(t.startsWith(n)||"!"!=n[0]&&gt(t,n)){e=!1;break}if("!"==n[0]&&!gt(t,n)){e=!0;break}}if(e)return!0}if(n)for(const e of le)if(e===u.extname(t).toLowerCase())return!0;return!1}function ue(t,e=!0){let n=null,r=!1;if(t.query.file){if(n=t.query.file,ce(n,e,!1))return["illegal file path"];n=u.join(o.tpmasterdir,n)}else if(t.query.url){if(n=t.query.url,n.includes(" "))return["url must not contain whitespace"];if(n.includes('"')||n.includes("'"))return["url must not contain single or double quotes"];r=!0}return n?[null,n,r]:["file unspecified"]}function fe(t){const e=t.split(/\r?\n/);if(e.length<=1||!e[0])return[null,[]];const n=e[0].split("\t"),r=[];for(let t=1;t<e.length;t++){if("#"==e[t][0])continue;const o=e[t].split("\t"),i={};for(let t=0;t<n.length;t++){const e=o[t];e&&(i[n[t]]=e)}r.push(i)}return[null,r]}async function de(){const t=await c.promises.readdir(o.cachedir_massSession);try{t.forEach((async t=>{const e=(await c.promises.stat(u.join(o.cachedir_massSession,t))).birthtime,n=new Date,r=new Date(e),i=o.features.massSessionDuration||30;Math.round((n.getTime()-r.getTime())/864e5)>i&&(await c.promises.copyFile(u.join(o.cachedir_massSession,t),u.join(o.cachedir_massSessionTrash,t)),await c.promises.unlink(u.join(o.cachedir_massSession,t)),console.log("File deleted: ",t,e))}))}catch(t){throw`Error: ${t}`}}function he(t,e){if(t.dbfile)try{console.log("Connecting",t.dbfile),t.newconn=x.connect_db(t.dbfile)}catch(e){throw"Error with "+t.dbfile+": "+e}if(t.snvindel_attributes)for(const e of t.snvindel_attributes)if(e.lst)for(const t of e.lst)t.get=t.get.toString();else e.get=e.get.toString();if(t.cohort){if(t.cohort.levels){if(!Array.isArray(t.cohort.levels))throw"cohort.levels must be array for "+t.genomename+"."+t.label;if(0==t.cohort.levels.length)throw"levels is blank array for cohort of "+t.genomename+"."+t.label;for(const e of t.cohort.levels)if(!e.k)throw".k key missing in one of the levels, .cohort, in "+t.genomename+"."+t.label}if(t.cohort.fromdb){if(!t.cohort.fromdb.sql)throw".sql missing from ds.cohort.fromdb in "+t.genomename+"."+t.label;const e=t.newconn.prepare(t.cohort.fromdb.sql).all();delete t.cohort.fromdb,t.cohort.raw=e,console.log(e.length+" rows retrieved for "+t.label+" sample annotation")}if(t.cohort.files){let e=[];for(const n of t.cohort.files){if(!n.file)throw".file missing from one of cohort.files[] for "+t.genomename+"."+t.label;const r=c.readFileSync(u.join(o.tpmasterdir,n.file),"utf8").trim();if(!r)throw n.file+" is empty for "+t.genomename+"."+t.label;e=[...e,...R.tsvParse(r)]}delete t.cohort.files,t.cohort.raw?t.cohort.raw=[...t.cohort.raw,...e]:t.cohort.raw=e,console.log(e.length+" rows retrieved for "+t.label+" sample annotation")}if(t.cohort.tosampleannotation){if(!t.cohort.tosampleannotation.samplekey)throw".samplekey missing from .cohort.tosampleannotation for "+t.genomename+"."+t.label;if(!t.cohort.key4annotation)throw".cohort.key4annotation missing when .cohort.tosampleannotation is on for "+t.genomename+"."+t.label}}if(!t.queries)throw".queries missing from dataset "+t.label+", "+t.genomename;if(!Array.isArray(t.queries))throw t.label+".queries is not array";for(const n of t.queries){const r=me(n,t,e);if(r)throw'Error parsing a query in "'+t.label+'": '+r}if(t.vcfinfofilter){const e=k.validate_vcfinfofilter(t.vcfinfofilter);if(e)throw t.label+": vcfinfofilter error: "+e}if(t.url4variant)for(const e of t.url4variant){if(!e.makelabel)throw"makelabel() missing for one item of url4variant from "+t.label;if(!e.makeurl)throw"makeurl() missing for one item of url4variant from "+t.label;e.makelabel=e.makelabel.toString(),e.makeurl=e.makeurl.toString()}}async function pe(t){const e=u.join(o.cachedir,t);try{await c.promises.stat(e)}catch(t){if("ENOENT"!=t.code)throw"error stating dir";try{await c.promises.mkdir(e)}catch(t){throw"cannot make dir"}}return e}function me(t,e,n){if(!t.name)return".name missing";if(t.dsblocktracklst){if(!Array.isArray(t.dsblocktracklst))return"dsblocktracklst not an array in "+e.label;for(const n of t.dsblocktracklst){if(!n.type)return"missing type for a blocktrack of "+e.label;if(!n.file&&!n.url)return"neither file or url given for a blocktrack of "+e.label}}else if(t.vcffile){const e=p.execSync(vt+" -H "+u.join(o.tpmasterdir,t.vcffile),{encoding:"utf8"}).trim();if(""==e)return"no meta lines in VCF file "+t.vcffile+" of query "+t.name;const[r,i,s,a]=q.vcfparsemeta(e.split("\n"));if(a)return"error parsing VCF meta lines of "+t.vcffile+": "+a.join("; ");t.vcf={vcfid:Math.random().toString(),info:r,format:i,samples:s},t.hlinfo&&(t.vcf.hlinfo=t.hlinfo,delete t.hlinfo),t.infopipejoin&&(t.vcf.infopipejoin=t.infopipejoin,delete t.infopipejoin);const l=p.execSync(vt+" -l "+u.join(o.tpmasterdir,t.vcffile),{encoding:"utf8"}).trim();if(""==l)return"tabix -l found no chromosomes/contigs in "+t.vcffile+" of query "+t.name;t.vcf.nochr=k.contigNameNoChr(n,l.split("\n"));let c=0;if(r)for(const t in r)c++;console.log("Parsed vcf meta from "+t.vcffile+": "+c+" INFO, "+s.length+" sample, "+(t.vcf.nochr?'no "chr"':'has "chr"'))}else{if(!t.makequery)return"do not know how to parse query: "+t.name;if(t.isgeneexpression){if(!t.config)return"config object missing for gene expression query of "+t.name;t.config.maf&&(t.config.maf.get=t.config.maf.get.toString())}}}async function ge(t,e,n){if((t.isMds2||t.isMds3||t.isMds)&&Q(t,n),t.assayAvailability){if(!t.assayAvailability.file)throw".assayAvailability.file missing";if(!t.assayAvailability.assays)throw".assayAvailability.assays[] missing";Object.freeze(t.assayAvailability.assays),t.assayAvailability.samples=new Map;for(const e of c.readFileSync(u.join(o.tpmasterdir,t.assayAvailability.file),{encoding:"utf8"}).trim().split("\n")){const[n,r]=e.split("\t");t.assayAvailability.samples.set(n,JSON.parse(r))}console.log(t.assayAvailability.samples.size+" samples with assay availability ("+t.label+")")}if(t.gene2mutcount){if(!t.gene2mutcount.dbfile)throw".gene2mutcount.dbfile missing";try{console.log("Connecting",t.gene2mutcount.dbfile),t.gene2mutcount.db=x.connect_db(t.gene2mutcount.dbfile),console.log("DB connected for "+t.label+": "+t.gene2mutcount.dbfile)}catch(t){throw"Error connecting db at ds.gene2mutcount.dbfile"}}if(t.sampleAssayTrack){if(!t.sampleAssayTrack.file)throw".file missing from sampleAssayTrack";t.sampleAssayTrack.samples=new Map;let e=0,n=new Set;for(const r of c.readFileSync(u.join(o.tpmasterdir,t.sampleAssayTrack.file),{encoding:"utf8"}).trim().split("\n")){if(!r)continue;if("#"==r[0])continue;const[o,i,s]=r.split("\t");if(!i||!s)continue;if(!t.sampleAssayTrack.samples.has(o)){if(t.cohort&&t.cohort.annotation&&!t.cohort.annotation[o]){n.add(o);continue}t.sampleAssayTrack.samples.set(o,[])}const a=JSON.parse(s);if(!k.tkt[a.type])throw"invalid type from a sample track: "+s;a.name||(a.name=o+" "+i),a.assayName=i,t.sampleAssayTrack.samples.get(o).push(a),e++}console.log(e+" assay-tracks from "+t.sampleAssayTrack.samples.size+" samples ("+t.label+")"),n.size&&console.log("Error: "+n.size+" samples with assay tracks are unannotated: "+[...n].join(" "))}if(t.singlesamplemutationjson){const e=t.singlesamplemutationjson;if(!e.file)throw".file missing from singlesamplemutationjson";e.samples={};let n=0;for(const t of c.readFileSync(u.join(o.tpmasterdir,e.file),{encoding:"utf8"}).trim().split("\n")){if(!t)continue;if("#"==t[0])continue;const[r,o]=t.split("\t");r&&o&&(n++,e.samples[r]=o)}console.log(n+" samples for disco plot")}if(t.cohort&&t.cohort.db&&t.cohort.termdb&&await K.init_db(t,Nt,St),t.cohort&&t.cohort.files){if(!Array.isArray(t.cohort.files))throw".cohort.files is not array";if(!t.cohort.tohash)throw".tohash() missing from cohort";if("function"!=typeof t.cohort.tohash)throw".cohort.tohash is not function";if(!t.cohort.samplenamekey)throw".samplenamekey missing";if(t.cohort.annotation={},t.cohort.mutation_signature){const e=t.cohort.mutation_signature;if(!e.sets)throw".mutation_signature.sets missing";for(const n in e.sets){const r=e.sets[n];if(r.name||(r.name=n),!r.signatures)throw".signatures{} missing from a signature set";if(r.samples){if(!r.samples.file)throw".samples.file missing from a signature set";const[e,n]=fe(c.readFileSync(u.join(o.tpmasterdir,r.samples.file),{encoding:"utf8"}).trim());r.samples.map=new Map;for(const e of n){const n=e[t.cohort.samplenamekey];if(!n)throw t.cohort.samplenamekey+" missing in file "+r.samples.file;r.samples.map.set(n,e);for(const t in r.signatures)if(e[t]){const o=Number.parseFloat(e[t]);if(Number.isNaN(o))throw"mutation signature value is not float: "+e[t]+" from sample "+n;r.samples.skipzero&&0==o?delete e[t]:e[t]=o}}}}}if(t.cohort.attributes){if(!t.cohort.attributes.lst)throw".lst[] missing for cohort.attributes";if(!Array.isArray(t.cohort.attributes.lst))return".cohort.attributes.lst is not array";for(const e of t.cohort.attributes.lst){if(!e.key)throw".key missing from one of the .cohort.attributes.lst[]";if(!e.label)throw".label missing from one of the .cohort.attributes.lst[]";if(!e.values)throw".values{} missing from "+e.label+" of .cohort.attributes.lst";for(const t in e.values)if(!e.values[t].label)throw".label missing from one value of "+e.label+" in .cohort.attributes.lst"}if(t.cohort.attributes.defaulthidden)for(const e in t.cohort.attributes.defaulthidden){const n=t.cohort.attributes.lst.find((t=>t.key==e));if(!n)throw"invalid defaulthidden key: "+e;for(const r in t.cohort.attributes.defaulthidden[e])if(!n.values[r])throw"invalid defaulthidden value "+r+" for "+e}}if(t.cohort.hierarchies){if(!t.cohort.hierarchies.lst)throw".lst[] missing from .cohort.hierarchies";if(!Array.isArray(t.cohort.hierarchies.lst))throw".cohort.hierarchies.lst is not array";for(const e of t.cohort.hierarchies.lst){if(!e.name)throw".name missing from one hierarchy";if(!e.levels)throw".levels[] missing from one hierarchy";if(!Array.isArray(e.levels))throw".levels is not array from one hierarchy";for(const t of e.levels)if(!t.k)throw".k missing from one level in hierarchy "+e.name}}if(t.cohort.sampleAttribute){if(!t.cohort.sampleAttribute.attributes)throw"attributes{} missing from cohort.sampleAttribute";for(const e in t.cohort.sampleAttribute.attributes){const n=t.cohort.sampleAttribute.attributes[e];if(!n.label)throw".label missing for key "+e+" from cohort.sampleAttribute.attributes";if(n.values)for(const t in n.values){const e=n.values[t];if("object"!=typeof e)throw'value "'+t+'" not pointing to {} from sampleAttribute';e.name||(e.name=t)}if(n.showintrack&&!n.isinteger&&!n.isfloat)throw n.label+": .showintrack requires .isinteger or .isfloat"}}if(t.cohort.scatterplot){if(!t.cohort.sampleAttribute)throw".sampleAttribute missing but required for .cohort.scatterplot";const e=t.cohort.scatterplot;if(!e.querykey)throw".querykey missing from .cohort.scatterplot";{if(!t.queries)throw".cohort.scatterplot.querykey in use but ds.queries{} missing";const n=t.queries[e.querykey];if(!n)throw"unknown query by .cohort.scatterplot.querykey: "+e.querykey;if(n.type!=k.tkt.mdssvcnv)throw"type is not "+k.tkt.mdssvcnv+" of the track pointed to by .cohort.scatterplot.querykey"}if(e.colorbygeneexpression){if(!e.colorbygeneexpression.querykey)throw"querykey missing from .cohort.scatterplot.colorbygeneexpression";if(!t.queries)throw".cohort.scatterplot.colorbygeneexpression in use but ds.queries{} missing";const n=t.queries[e.colorbygeneexpression.querykey];if(!n)throw"unknown query by .cohort.scatterplot.colorbygeneexpression.querykey: "+e.colorbygeneexpression.querykey;if(!n.isgenenumeric)throw"isgenenumeric missing from the track pointed to by .cohort.scatterplot.colorbygeneexpression.querykey"}if(e.tracks,!e.x)throw".x missing from .cohort.scatterplot";if(!e.x.attribute)throw".attribute missing from .cohort.scatterplot.x";const n=t.cohort.sampleAttribute.attributes[e.x.attribute];if(!n)throw"scatterplot.x.attribute is not defined in sampleAttribute";if(!n.isfloat)throw'scatterplot.x is not "isfloat"';if(!e.y)throw".y missing from .cohort.scatterplot";if(!e.y.attribute)throw".attribute missing from .cohort.scatterplot.y";const r=t.cohort.sampleAttribute.attributes[e.y.attribute];if(!r)throw"scatterplot.y.attribute is not defined in sampleAttribute";if(!r.isfloat)throw'scatterplot.y is not "isfloat"';if(e.colorbyattributes)for(const n of e.colorbyattributes){if(!n.key)throw".key missing from one of scatterplot.colorbyattributes";const e=t.cohort.sampleAttribute.attributes[n.key];if(!e)throw"unknown attribute by key "+n.key+" from scatterplot.colorbyattributes";n.label=e.label,n.values=e.values}}for(const e of t.cohort.files){if(!e.file)throw".file missing from one of .cohort.files";const[n,r]=fe(c.readFileSync(u.join(o.tpmasterdir,e.file),{encoding:"utf8"}).trim());if(n)throw'cohort annotation file "'+e.file+'": '+n;console.log(t.label+": "+r.length+" samples loaded from annotation file "+e.file),r.forEach((e=>{for(const n in e){let r;t.cohort.sampleAttribute&&(r=t.cohort.sampleAttribute.attributes[n]),r||t.cohort.termdb&&t.cohort.termdb.termjson&&t.cohort.termdb.termjson.map&&(r=t.cohort.termdb.termjson.map.get(n)),r&&(r.isfloat?e[n]=Number.parseFloat(e[n]):r.isinteger&&(e[n]=Number.parseInt(e[n])))}t.cohort.tohash(e,t)}))}if(t.cohort.annorows=Object.values(t.cohort.annotation),console.log(t.label+": total samples from sample table: "+t.cohort.annorows.length),t.cohort.survivalplot){const e=t.cohort.survivalplot;if(!e.plots)throw".plots{} missing from survivalplot";e.init={plottypes:[]};for(const t in e.plots){const n=e.plots[t];if(!n.name)throw".name missing from survivalplot "+t;if(!n.serialtimekey)throw".serialtimekey missing from survivalplot "+t;if(!n.iscensoredkey)throw".iscensoredkey missing from survivalplot "+t;if(!n.timelabel)throw".timelabel missing from survivalplot "+t;n.key=t,e.init.plottypes.push({key:t,name:n.name,timelabel:n.timelabel})}if(e.samplegroupattrlst){e.init.samplegroupings=[];for(const n of e.samplegroupattrlst){if(!n.key)throw".key missing from an attr of samplegroupattrlst for survival";const r=t.cohort.sampleAttribute.attributes[n.key];if(!r)throw'unknown attribute key "'+n.key+'" from survival samplegroupattrlst';const o=new Map;for(const r in t.cohort.annotation){const i=t.cohort.annotation[r],s=i[n.key];if(null==s)continue;let a=!1;for(const t in e.plots)if(null!=i[e.plots[t].serialtimekey]){a=!0;break}a&&(o.has(s)?o.set(s,o.get(s)+1):o.set(s,1))}if(0==o.size)throw'no value found for "'+n.key+'" from survival samplegroupattrlst';const i=[];for(const[t,e]of o)i.push({value:t,count:e});e.init.samplegroupings.push({key:n.key,label:r.label,values:i})}}}}if(t.mutationAttribute){if(!t.mutationAttribute.attributes)throw"attributes{} missing from mutationAttribute";for(const e in t.mutationAttribute.attributes){const n=t.mutationAttribute.attributes[e];if(!n.label)throw".label missing for key "+e+" from mutationAttribute.attributes";if(!n.appendto_link&&n.values)for(const t in n.values){if(!n.values[t].name)throw".name missing for value "+t+" of key "+e+" from mutationAttribute.attributes"}}}if(t.alleleAttribute){if(!t.alleleAttribute.attributes)throw"attributes{} missing from alleleAttribute";for(const e in t.alleleAttribute.attributes){const n=t.alleleAttribute.attributes[e];if(!n.label)throw".label missing for key "+e+" from alleleAttribute.attributes";if(!n.isnumeric){if(!n.values)throw".values{} missing for non-numeric key "+e+" from alleleAttribute.attributes";for(const t in n.values){if(!n.values[t].name)throw".name missing for value "+t+" of key "+e+" from alleleAttribute.attributes"}}}}if(t.locusAttribute){if(!t.locusAttribute.attributes)throw"attributes{} missing from locusAttribute";for(const e in t.locusAttribute.attributes){const n=t.locusAttribute.attributes[e];if(!n.label)throw".label missing for key "+e+" from locusAttribute.attributes";if(!n.isnumeric&&!n.appendto_link){if(!n.values)throw".values{} missing for non-numeric key "+e+" from locusAttribute.attributes";for(const t in n.values){if(!n.values[t].name)throw".name missing for value "+t+" of key "+e+" from locusAttribute.attributes"}}}}if(t.queries)for(const r in t.queries){if(n.remove_queries&&-1!=n.remove_queries.indexOf(r)){delete t.queries[r];continue}const o=t.queries[r];if(n.hide_queries&&-1!=n.hide_queries.indexOf(r)&&(o.hideforthemoment=1),o.istrack){if(!o.type)throw".type missing for track query "+r;if(o.viewrangeupperlimit&&!Number.isInteger(o.viewrangeupperlimit))throw".viewrangeupperlimit should be integer for track query "+r;if(o.type==k.tkt.mdsjunction){const n=ve(o,t,e);if(n)throw r+" (mdsjunction) error: "+n}else if(o.type==k.tkt.mdscnv){const n=we(o,t,e);if(n)throw r+" (mdscnv) error: "+n}else if(o.type==k.tkt.mdssvcnv){const n=xe(o,t,e);if(n)throw r+" (svcnv) error: "+n}else{if(o.type!=k.tkt.mdsvcf)throw"unknown track type for a query: "+o.type+" "+r;{const n=await qe(o,t,e);if(n)throw r+" (vcf) error: "+n}}ye(o,t)}else{if(!o.isgenenumeric)throw"unknown type of query from "+r;{const n=ke(o,t,e);if(n)throw r+" (genenumeric) error: "+n}}}if(t.track&&await K.init_track(t,e),t.annotationsampleset2matrix){if(!t.cohort)throw"ds.cohort misssing when annotationsampleset2matrix is in use";if(!t.cohort.annotation)throw"ds.cohort.annotation misssing when annotationsampleset2matrix is in use";if(!t.queries)throw"ds.queries misssing when annotationsampleset2matrix is in use";if(!t.annotationsampleset2matrix.key)throw".key STR missing in annotationsampleset2matrix";if(!t.annotationsampleset2matrix.groups)throw".groups{} missing in annotationsampleset2matrix";if("object"!=typeof t.annotationsampleset2matrix.groups)throw"ds.annotationsampleset2matrix.groups{} not an object";for(const e in t.annotationsampleset2matrix.groups){const n=t.annotationsampleset2matrix.groups[e];if(!n.groups||!Array.isArray(n.groups)||0==n.groups.length)throw".groups[] must be nonempty array in "+e;for(const r of n.groups){if(!r.name)throw".name missing from one of .groups[] in "+e;const n=r.matrixconfig;if(!n)throw".matrixconfig missing from one of .groups[] of "+e;if(!n.features)throw".features[] missing from group "+e;if(!Array.isArray(n.features))throw".features[] should be array from group "+e;if(0==n.features.length)throw".features[] zero length from group "+e;for(const r of n.features){if(t.annotationsampleset2matrix.commonfeatureattributes)for(const e in t.annotationsampleset2matrix.commonfeatureattributes)null==r[e]&&(r[e]=t.annotationsampleset2matrix.commonfeatureattributes[e]);if(!r.ismutation)return"unknown feature type from group "+e;if(!r.position)throw"position missing from feature "+JSON.stringify(r)+" from group "+e;if(!r.querykeylst)throw".querykeylst[] missing from ismutation feature from group "+e;if(!Array.isArray(r.querykeylst))throw".querykeylst[] not an array from ismutation feature from group "+e;if(0==r.querykeylst.length)throw".querykeylst[] zero length from ismutation feature from group "+e;for(const n of r.querykeylst)if(!t.queries[n])throw'unknown query key "'+n+'" from ismutation feature of group '+e}if(!n.limitsamplebyeitherannotation)throw".limitsamplebyeitherannotation[] missing from group "+e;if(!Array.isArray(n.limitsamplebyeitherannotation))throw".limitsamplebyeitherannotation[] should be array from group "+e;if(0==n.limitsamplebyeitherannotation.length)throw".limitsamplebyeitherannotation[] zero length from group "+e;for(const t of n.limitsamplebyeitherannotation){if(!t.key)throw"key missing from one of limitsamplebyeitherannotation from group "+e;if(!t.value)throw"value missing from one of limitsamplebyeitherannotation from group "+e}}}delete t.annotationsampleset2matrix.commonfeatureattributes}}function ye(t,e){if(t.groupsamplebyattr){t.groupsamplebyattr.key2group=new Map;for(const n in e.cohort.annotation)Zt(n,[],t.groupsamplebyattr.key2group,[],e,t)}}function ve(t,e,n){if(t.readcountCutoff&&(!Number.isInteger(t.readcountCutoff)||t.readcountCutoff<1))return"readcountCutoff must be positive integer";let r;if(t.file){const[e,n]=se(t.file);if(e)return"tabix file error: "+e;t.file=n,r=n}else{if(!t.url)return"no file or url given for mdsjunction "+t.name;r=t.url}const o={encoding:"utf8"};const i=p.execSync(vt+" -H "+r,o).trim();if(i){const n=i.split("\n");if(1!=n.length)return"mdsjunction file has multiple header lines (begin with #), but should have just 1";const r=n[0].split("\t");if(r[5]){t.samples=r.slice(5),t.attributeSummary=be(t.samples,e),t.hierarchySummary=_e(t.samples,e);for(const e in t.hierarchySummary){let n=0;for(const r in t.hierarchySummary[e])n++;console.log(n+" "+e+" hierarchy levels for "+t.name)}}}{const e=p.execSync(vt+" -l "+r,o).trim();if(!e)return"no chromosomes found";t.nochr=k.contigNameNoChr(n,e.split("\n"))}if(console.log("(mdsjunction) "+t.name+": "+(t.samples?t.samples.length:0)+" samples, "+(t.nochr?'no "chr"':'has "chr"')),!t.infoFilter)return".infoFilter{} missing";if(!t.infoFilter.lst)return".lst[] missing from .infoFilter";for(const e of t.infoFilter.lst){if(!e.key)return".key missing from one of infoFilter";if(!e.label)return".label missing from one of infoFilter";if(!e.categories)return".categories missing from one of infoFilter";for(const t in e.categories){if(!e.categories[t].label)return".label missing from one category of "+e.label;if(!e.categories[t].color)return".color missing from on category of "+e.label}if(e.hiddenCategories){for(const t in e.hiddenCategories)if(!e.categories[t])return"invalid hidden key "+t+" of "+e.label}else e.hiddenCategories={}}if(!t.singlejunctionsummary)return".singlejunctionsummary missing but is currently required from 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i=t.diff_score_plotwidth/(r-o),s=r*i-o*i,a=p(s*t.devicePixelRatio,e.canvasheight*t.devicePixelRatio),l=a.getContext("2d");t.devicePixelRatio>1&&l.scale(t.devicePixelRatio,t.devicePixelRatio);const c=n.map((t=>t.__tempscore)),u=e.canvasheight/c.length;let f=0;const d=e.stackspace/e.canvasheight;for(const t of c){let e=0;for(const n of t)"alt0"==n?l.fillStyle=W:"ref"==n?l.fillStyle=X:"alt1"==n?l.fillStyle=J:"alt2"==n?l.fillStyle=V:"alt3"==n?l.fillStyle=Y:"alt4"==n?l.fillStyle=Q:"alt5"==n&&(l.fillStyle=K),l.fillRect(i*e,f*u,i,u-d*u),e+=1;f+=1}return{height:e.canvasheight,width:s,src:a.toDataURL(),read_height:u}}function at(t,e,n,r){for(const o of n)for(const n of o.segments)if(!(n.ridx!=t||Math.max(n.segstart,e.start)>Math.min(n.segstop,e.stop)))for(const t of n.boxes)if(e.ntwidth>=1){if(("S"==t.opr||"X"==t.opr)&&t.s)for(let e=0;e<t.s.length;e++){const n=t.start+e,o=r.find((t=>t.position==n));if(!o)continue;const i=t.s[e];o[i]=1+(o[i]||0),"S"==t.opr&&o.total++}}else if("S"==t.opr){const 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c=m(k,["-i","-","-t","DNA","--outfmt=clu","--wrap=5000","--maxnumseq="+(e+1),"--maxseqlen=1000"]),u=[],d=[];f.from(t).pipe(c.stdin),c.stdout.on("data",(t=>u.push(t))),c.stderr.on("data",(t=>d.push(t))),c.on("error",(t=>{console.log("stderr (clustalo):",d),l(t)})),c.on("close",(t=>{let e=0;const c=[],f={final_read_align:[],qual_r:[],qual_g:[],qual_b:[]};let d=0;for(const t of u.toString().split("\n"))if(t.includes("seq ")){let n=0,l="",u=0,h="";0!=e&&a?h=r.split("\n")[e-1].split(","):a||(h=r.split("\n")[e].split(","));let p="",m="",g="";for(const r of t.replace("seq ",""))if(","!=r){if("-"!=r){if(n+=1,l+=r,0==e&&a)c.push(r);else if(r==c[u]&&a||!a){const t=S(h[n-1]/tt).replace("rgb(","").replace(")","").split(",");p+=t[0]+",",m+=t[1]+",",g+=t[2]+","}else if(r!=c[u]&&a){const t=E(h[n-1]/tt).replace("rgb(","").replace(")","").split(",");p+=t[0]+",",m+=t[1]+",",g+=t[2]+","}}else n>0&&n<t.replace(/-/g,"").replace(/,/g,"").replace("seq ","").length?(l+=r,0==e&&(c.push(r),u<o&&(d+=1))):(l+=" 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d.get_lines_bigfile({isbam:!0,args:n,dir:e.dir,callback:(n,r)=>{if(!(1024&n.split("\t")[1]&&e.drop_pcrduplicates)){if(e.downsample){const t=e.downsample;if(t.pointer++,t.pointer>=t.keep&&t.pointer<t.keep+t.skip)return;t.pointer>=t.keep+t.skip&&(t.pointer=0)}t.lines.push(n)}}})}async function dt(t,e){const n=[],r=["depth","-r",(t.nochr?e.chr.replace("chr",""):e.chr)+":"+(e.start+1)+"-"+e.stop,"-g","DUP",t.file||t.url];if(t.drop_pcrduplicates&&(r.push("-G"),r.push("0x400")),await d.get_lines_bigfile({isbam:!0,args:r,dir:t.dir,callback:t=>{const r=t.split("\t"),o=Number.parseInt(r[1])-1,i=Number.parseInt(r[2]);if(e.ntwidth>=1)return void n.push({position:o,total:i});const s=Math.floor((o-e.start)*e.ntwidth);n[s]||(n[s]={position:o,sum:0,count:0}),n[s].sum+=i,n[s].count++}}),e.ntwidth<1)for(const t of n)t&&(t.total=t.sum/t.count,delete t.sum,delete t.count);return n}async function ht(t,e){for(const t of e.regions)t.lines.length>0&&t.ntwidth>=.9&&(t.to_checkmismatch=!0,t.referenceseq=await vt(e.genome,t.chr+":"+(t.start+1)+"-"+t.stop));for(const n of t)for(const t of n.segments){const n=e.regions[t.ridx];if(!n.to_checkmismatch)continue;const r=[];for(const e of t.boxes)null!=e.cidx&&"M"==e.opr&&(e.s=t.seq.substr(e.cidx,e.len),xt(r,n,e,e.s));r.length&&t.boxes.push(...r)}for(const t of e.regions)delete t.to_checkmismatch,delete t.referenceseq}function pt(t,e){if(!t.asPaired){const n=[];for(let r=0;r<t.regions.length;r++){const o=t.regions[r];for(const i of e.templates){i.ridx=r;const e=mt(i,o,t);e&&n.push({x1:e.x1,x2:e.x2,__tempscore:e.tempscore,segments:[e]})}}return n}const n=new Map;for(let r=0;r<t.regions.length;r++){const o=t.regions[r];for(const i of e.templates){i.ridx=r;const e=mt(i,o,t);if(!e||!e.qname)continue;const s=n.get(e.qname);s?(s.segments.push(e),s.x2=Math.max(s.x2,e.x2)):n.set(e.qname,{x1:Math.max(e.x1,o.x),x2:Math.min(e.x2,o.x+o.width),__tempscore:e.tempscore,segments:[e]})}}return[...n.values()]}function mt(t,e,n){const{sam_info:r,tempscore:o,ridx:i,keepallboxes:s,keepmatepos:a,keepunmappedread:l}=t,c=r.trim().split("\t");if(c.length<11)return;const u=c[0],f=c[1],d=Number.parseInt(c[3]),h=c[5],p=c[6],m=c[7],g=Number.parseInt(c[8]),y=c[9],v=c[10];if(Number.isNaN(d)||d<=0)return;const b=d-1,_={qname:u,segstart:b,segstart_original:b,segstop:b,boxes:[],forward:!(16&f),ridx:i,seq:y,qual:v,cigarstr:h,tlen:g,flag:f,tempscore:o};if(function(t,e,n,r,o,i){const s=t.flag;if(!(1&s))return;64&s?t.isfirst=!0:128&s&&(t.islast=!0);if("="!=e&&"*"!=e&&e!=r.chr)return t.rnext=e,void(t.pnext=n);if(8&s)return void(t.discord_unmapped2=!0);32&s&&!(16&s)&&64&s||16&s&&!(32&s)&&128&s||16&s&&!(32&s)&&64&s||32&s&&!(16&s)&&128&s||(t.discord_orientation=!0,o&&(16&s?32&s?t.discord_orientation_direction="R1R2":n>i&&(t.discord_orientation_direction="R1F2"):32&s?n<i&&(t.discord_orientation_direction="R1F2"):t.discord_orientation_direction="F1F2")),2&s||(t.discord_wrong_insertsize=!0,o&&(t.pnext=n))}(_,p,m,e,a,d),4&f)return l?(_.boxes.push({opr:h,start:b,len:y.length,cidx:0,qual:v}),_.discord_unmapped1=!0,_):void 0;if("*"!=h){let t=b,r=0,o=0;for(let n=0;n<h.length;n++){const i=h[n];if(i.match(/[0-9]/))continue;const a=Number.parseInt(h.substring(r,n));if("H"!=i)if("N"==i||"P"==i||"D"==i||(o+=a),r=n+1,"="!=i&&"M"!=i)if("I"!=i)if("N"!=i&&"D"!=i)if("X"!=i)if("S"!=i){if("P"!=i)console.log("unknown cigar: "+i);else if(s||t>e.start&&t<e.stop){const e={opr:"P",start:t,len:a,cidx:o-a};_.boxes.push(e)}}else{const n={opr:i,start:t,len:a,cidx:o-a};0==_.boxes.length?(n.start-=a,(s||Math.max(t,e.start)<=Math.min(t+a-1,e.stop))&&_.boxes.push(n)):_.boxes.push(n)}else{if(s||Math.max(t,e.start)<Math.min(t+a-1,e.stop)){const e={opr:i,start:t,len:a,cidx:o-a};_.boxes.push(e)}t+=a}else(t>=e.start&&t<=e.stop||t+a-1>=e.start&&t+a-1<=e.stop||s)&&_.boxes.push({opr:i,start:t,len:a}),t+=a;else(s||t>e.start&&t<e.stop)&&a*e.ntwidth>=1&&_.boxes.push({opr:"I",start:t,len:a,cidx:o-a});else(s||Math.max(t,e.start)<=Math.min(t+a-1,e.stop))&&_.boxes.push({opr:i,start:t,len:a,cidx:o-a}),t+=a;else _.boxes.push({opr:i,start:t,len:a,cidx:o-a}),r=n+1}if(0==_.boxes.length)return void(n&&n.readcount_skipped++);_.segstop=t,_.x1=e.x+e.scale(_.boxes[0].start),_.x2=e.x+e.scale((w=_.boxes,Math.max(...w.map((t=>t.start+t.len)))))}var w;return _}async function gt(t,e,n){const[r,o]=function(t,e){let n=(e.groups.length>1?750:rt)/t;return n>10?[Math.min(15,Math.floor(n)),1]:n>7?[Math.floor(n),1]:n>3?[Math.ceil(n),0]:n>1?[Math.floor(n),0]:[n,0]}(t.stacks.length,e);t.stackheight=r,t.stackspace=o;for(const e of t.regions)e.to_printnt=t.stackheight>7&&e.ntwidth>=7,e.to_qual=e.ntwidth>=1;if(t.stacks.length&&(t.stackheight>=7&&n.length<2e3?t.returntemplatebox=[]:t.partstack||(t.allowpartstack=!0)),t.stackheight>=7){let e=0;for(const t of n)for(const n of t.segments)e=Math.max(e,n.x2-n.x1);e>.7*t.stackheight&&(t.canClipArrowhead=!0)}}function yt(t,e,n){if(e.asPaired){t.stacks=[];const r=[],o=[];for(const t of n){let n=t.segments[0].ridx;1==t.segments.length||2==t.segments.length&&t.segments[0].ridx==t.segments[1].ridx?(t.x1=Math.max(e.regions[n].x,t.x1),t.x2=Math.min(e.regions[n].x+e.regions[n].width,t.x2),r.push(t)):2==t.segments.length&&t.segments[0].ridx!=t.segments[1].ridx&&(t.x1=t.x1,t.x2=t.x2,o.push(t))}if(r.sort(((t,e)=>t.x1-e.x1)),o.sort(((t,e)=>t.x1-e.x1)),o.length>0){const t=[],e=[],i=o[0];for(const n of r)n.x1<i.x1&&n.x2<i.x1?t.push(n):e.push(n);n=[...t,...o,...e]}for(const r of n){let n=r.segments[0].ridx,o=null;if(!e.variant)for(let i=0;i<t.stacks.length;i++){if(r.x2==e.regions[n].x+e.regions[n].width&&t.stacks[i]<r.x1){o=i,t.stacks[i]=r.x2;break}if(t.stacks[i]+e.stacksegspacing<r.x1){o=i,t.stacks[i]=r.x2;break}}null==o&&(o=t.stacks.length,t.stacks[o]=r.x2),r.y=o}}else{n.sort(((t,e)=>t.x1-e.x1)),t.stacks=[];for(let r=0;r<e.regions.length;r++)for(const o of n)if(o.segments[0].ridx==r){let n=null;if(!e.variant&&!e.sv)for(let i=0;i<t.stacks.length;i++)if(t.stacks[i]+e.stacksegspacing<o.x1&&t.stacks[i]+e.stacksegspacing<e.regions[r].x+e.regions[r].width){n=i,t.stacks[i]=o.x2;break}null==n&&(n=t.stacks.length,t.stacks[n]=o.x2),o.y=n}}return n=function(t,e,n){if(!t.partstack)return e;const r=e.filter((e=>e.y>=t.partstack.start&&e.y<=t.partstack.stop));r.forEach((e=>e.y-=t.partstack.start)),e=r,t.stacks=[];for(let e=t.partstack.start;e<=t.partstack.stop;e++)t.stacks.push(0);return 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e.seq,delete e.qual}}}function _t(t){if("*"==t)return null;const e=[];for(let n=0;n<t.length;n++){const r=t[n].charCodeAt(0)-33;e.push(r)}return e}function wt(t,e){if(2==t.segments.length){const[n,r]=t.segments;return n.x2>r.x1?(r.shiftdownrow=1,2*e):e}console.log("more than 2 segments",t.segments.length);const n=[];for(const e of t.segments){let t=null;for(let r=0;r<n.length;r++)if(n[r]<e.x1){t=r,n[r]=e.x2;break}null==t&&(t=n.length,n[t]=e.x2),e.shiftdownrow=t}return e*n.length}function xt(t,e,n,r){for(let o=0;o<r.length;o++){if(n.start+o<e.start||n.start+o>e.stop)continue;const i=r[o];if(e.referenceseq[n.start+o-e.start]!=i.toUpperCase()){const e={opr:"X",start:n.start+o,len:1,s:i,cidx:n.cidx+o};t.push(e)}}}function kt(t,e,n,r){if(n.returntemplatebox){const t=n.regions[e.segments[0].ridx];let o;if(t.width=n.widths[e.segments[0].ridx],r.asPaired)if(2==e.segments.length)o=e.segments[0].ridx!=e.segments[1].ridx?{qname:e.segments[0].qname,x1:e.x1,x2:e.x2,y1:e.y,y2:e.y+(e.height||n.stackheight),start:Math.min(...e.segments.map((t=>t.segstart))),stop:Math.max(...e.segments.map((t=>t.segstop))),multi_region:!0}:{qname:e.segments[0].qname,x1:Math.max(t.x,e.x1),x2:Math.min(e.x2,t.width),y1:e.y,y2:e.y+(e.height||n.stackheight),start:Math.min(...e.segments.map((t=>t.segstart))),stop:Math.max(...e.segments.map((t=>t.segstop)))};else{const t=e.segments[0],r=n.regions[t.ridx];r.width=n.widths[t.ridx],o={qname:e.segments[0].qname,x1:Math.max(r.x,e.x1),x2:Math.min(e.x2,r.width),y1:e.y,y2:e.y+(e.height||n.stackheight),start:Math.min(...e.segments.map((t=>t.segstart))),stop:Math.max(...e.segments.map((t=>t.segstop)))}}else o={qname:e.segments[0].qname,x1:Math.max(t.x,e.x1),x2:Math.min(e.x2,t.x+t.width),y1:e.y,y2:e.y+(e.height||n.stackheight),start:Math.min(...e.segments.map((t=>t.segstart))),stop:Math.max(...e.segments.map((t=>t.segstop)))},e.segments[0].isfirst&&(o.isfirst=!0),e.segments[0].islast&&(o.islast=!0);n.returntemplatebox.push(o)}for(let o=0;o<e.segments.length;o++){const i=e.segments[o],s=n.regions[i.ridx];if(s.width=n.widths[i.ridx],0==o){qt(t,i,e.y,n,r);continue}const a=e.segments[o-1],l=n.regions[a.ridx];if(l.width=n.widths[a.ridx],a.x2<=i.x1||e.segments[0].ridx!=e.segments[1].ridx){qt(t,i,e.y,n,r);const o=Math.floor(e.y+n.stackheight/2)+.5;if(t.strokeStyle=n.stackheight<=2?G:q,t.setLineDash([5,3]),t.beginPath(),l.x==s.x?(t.moveTo(a.x2,o),t.lineTo(i.x1,o)):l.x<a.x2&&i.x1<s.width&&(t.moveTo(Math.min(a.x2,l.width),o),t.lineTo(Math.max(i.x1,s.x),o)),t.stroke(),n.overlapRP_hlline){const r=a.boxes.reduce(((t,e)=>t.start+t.len>e.start+e.len?t:e));if(r.start+r.len==i.boxes[0].start){t.strokeStyle=U,t.setLineDash([]),t.beginPath();const r=Math.floor(i.x1)+.5;t.moveTo(r,e.y),t.lineTo(r,e.y+n.stackheight),t.stroke()}}}else if(n.overlapRP_multirows){if(qt(t,i,e.y+n.stackheight,n,r),n.overlapRP_hlline){const r=Math.floor(e.y+n.stackheight)+.5;t.strokeStyle=U,t.setLineDash([]),t.beginPath(),l.x<=a.x2&&i.x1<=s.width&&(t.moveTo(Math.max(i.x1,s.x),r),t.lineTo(Math.min(a.x2,l.width),r)),t.stroke()}}else qt(t,i,e.y,n,r)}null!=e.__tempscore&&x.features.indel_read_alignment_scores&&(t.fillStyle="blue",t.font=n.stackheight+"pt Arial",t.fillText(e.__tempscore,r.regions[0].width-100,e.y+n.stackheight/2))}function qt(t,e,n,r,o){const i=r.regions[e.ridx];i.width=r.widths[e.ridx];for(const o of e.boxes){const s=i.x+i.scale(o.start);if("P"!=o.opr&&"H"!=o.opr&&"I"!=o.opr)if("D"!=o.opr&&"N"!=o.opr)if("*"!=o.opr){if("X"!=o.opr&&"S"!=o.opr){if("M"!=o.opr&&"="!=o.opr)throw"unknown opr at rendering: "+o.opr;if(i.to_qual&&o.qual){let a=s;o.qual.forEach((o=>{e.rnext?t.fillStyle=M(o/tt):e.discord_orientation?t.fillStyle=B(o/tt):e.discord_wrong_insertsize?t.fillStyle=C(o/tt):e.discord_unmapped2?t.fillStyle=L(o/tt):t.fillStyle=S(o/tt),a+i.ntwidth+et<i.width&&i.x<=a?t.fillRect(a,n,i.ntwidth+et,r.stackheight):a<i.width&&a+i.ntwidth+et>=i.width&&i.x<=a?t.fillRect(a,n,i.width-a,r.stackheight):a<=i.x&&a+i.ntwidth+et>i.x&&t.fillRect(i.x,n,i.ntwidth+et+a-i.x,r.stackheight),a+=i.ntwidth}))}else o.qual?e.rnext?t.fillStyle=A:e.discord_orientation?t.fillStyle=D:e.discord_wrong_insertsize?t.fillStyle=T:e.discord_unmapped2?t.fillStyle=F:t.fillStyle=q:i.to_printnt?t.fillStyle="white":e.rnext?t.fillStyle=A:e.discord_orientation?t.fillStyle=D:e.discord_wrong_insertsize?t.fillStyle=T:e.discord_unmapped2?t.fillStyle=F:t.fillStyle=q,s+o.len*i.ntwidth+et<i.width&&s<i.width&&i.x<s+et?t.fillRect(s,n,o.len*i.ntwidth+et,r.stackheight):s+o.len*i.ntwidth+et<i.width&&i.x>=s?t.fillRect(i.x,n,o.len*i.ntwidth+et+s-i.x,r.stackheight):s+o.len*i.ntwidth+et>=i.width&&i.x<s?t.fillRect(s,n,i.width-s,r.stackheight):s+o.len*i.ntwidth+et>=i.width&&i.x>=s&&t.fillRect(i.x,n,i.width-s,r.stackheight);if(i.to_printnt){t.font=Math.min(i.ntwidth,r.stackheight-2)+"pt Arial",o.qual?t.fillStyle="white":t.fillStyle="black";for(let e=0;e<o.s.length;e++)s+i.ntwidth*(e+.5)<i.width&&s<i.width&&i.x<=s+i.ntwidth*(e+.5)&&t.fillText(o.s[e],s+i.ntwidth*(e+.5),n+r.stackheight/2)}}else if(i.to_qual&&o.qual){i.to_printnt&&(t.font=Math.min(i.ntwidth,r.stackheight-2)+"pt Arial");let e=s;for(let s=0;s<o.qual.length;s++){const a=o.qual[s]/tt;t.fillStyle="S"==o.opr?P(a):E(a),e+i.ntwidth+et<i.x+i.width&&i.x<=e?t.fillRect(e,n,i.ntwidth+et,r.stackheight):e<i.x+i.width&&e+i.ntwidth+et>=i.x+i.width&&i.x<=e?t.fillRect(e,n,i.width+i.x-e,r.stackheight):e<=i.x&&e+i.ntwidth+et>i.x&&t.fillRect(i.x,n,i.ntwidth+et+e-i.x,r.stackheight),i.to_printnt&&(o.qual?t.fillStyle="white":t.fillStyle="black",e+i.ntwidth/2<i.width&&e<i.width&&i.x<=e+i.ntwidth/2&&t.fillText(o.s[s],e+i.ntwidth/2,n+r.stackheight/2)),e+=i.ntwidth}}else if(t.fillStyle="S"==o.opr?R:j,s+o.len*i.ntwidth+et<i.width&&i.x<s?t.fillRect(s,n,o.len*i.ntwidth+et,r.stackheight):s+o.len*i.ntwidth+et<i.width&&i.x>=s?t.fillRect(i.x,n,o.len*i.ntwidth+et+s-i.x,r.stackheight):s+o.len*i.ntwidth+et<=i.width&&i.x<s&&t.fillRect(s,n,i.width-s,r.stackheight),i.to_printnt&&!o.qual){t.font=Math.min(i.ntwidth,r.stackheight-2)+"pt Arial",o.qual?t.fillStyle="white":t.fillStyle="black";for(let e=0;e<o.s.length;e++)s+i.ntwidth*(e+.5)<i.width&&s<i.width&&i.x<=s+i.ntwidth*(e+.5)&&t.fillText(o.s[e],s+i.ntwidth*(e+.5),n+r.stackheight/2)}}else{if(i.to_qual&&o.qual){let a=s;o.qual.forEach((o=>{e.discord_unmapped2&&(t.fillStyle=L(o/tt)),t.fillRect(a,n,i.ntwidth+et,r.stackheight),a+=i.ntwidth}))}else e.discord_unmapped2&&(t.fillStyle=F),t.fillRect(s,n,o.len*i.ntwidth+et,r.stackheight);i.to_printnt&&(t.font=Math.min(i.ntwidth,r.stackheight-2)+"pt Arial")}else{"D"==o.opr?t.strokeStyle="black":t.strokeStyle=r.stackheight<=2?G:q,t.setLineDash([]);const e=Math.floor(n+r.stackheight/2)+.5;if(t.beginPath(),t.moveTo(Math.max(s,i.x),e),t.lineTo(Math.min(s+o.len*i.ntwidth,i.x+i.width),e),t.stroke(),r.stackheight>7){const e=Math.max(i.x,s),a=Math.min(i.x+i.width,s+o.len*i.ntwidth);if(a-e>=50){const s=Math.min(10,Math.max(7,r.stackheight-2));t.font=s+"pt Arial";const l=t.measureText(o.len+" bp").width;l<a-e-20&&(t.fillStyle="white",(a+e)/2+l/2<i.width&&i.x<(a+e)/2-l/2?(t.fillRect((a+e)/2-l/2,n,l,r.stackheight),t.fillStyle=q,t.fillText(o.len+" bp",(a+e)/2,n+r.stackheight/2)):(a+e)/2+l/2<i.width&&i.x>=(a+e)/2-l/2?(t.fillRect(i.x,n,l+(a+e)/2-l/2-i.x,r.stackheight),t.fillStyle=q,t.fillText(o.len+" bp",(a+e)/2,n+r.stackheight/2)):(a+e)/2+l/2>=i.width&&i.x<(a+e)/2-l/2&&(t.fillRect((a+e)/2-l/2,n,i.width-(a+e)/2+l/2,r.stackheight),t.fillStyle=q,t.fillText(o.len+" bp",(a+e)/2,n+r.stackheight/2)))}}}}!function(t,e,n,r,o){if(!n.canClipArrowhead)return;if(e.x2-e.x1<5)return;if(e.forward){const i=Math.ceil(e.x2+et);i<=r.width+n.stackheight/2&&(t.fillStyle="white",t.beginPath(),t.moveTo(i-n.stackheight/2,o),t.lineTo(i,o),t.lineTo(i,o+n.stackheight/2),t.lineTo(i-n.stackheight/2,o),t.closePath(),t.fill(),t.beginPath(),t.moveTo(i-n.stackheight/2,o+n.stackheight),t.lineTo(i,o+n.stackheight),t.lineTo(i,o+n.stackheight/2),t.lineTo(i-n.stackheight/2,o+n.stackheight),t.closePath(),t.fill())}else{const i=e.x1;i>=r.x&&(t.fillStyle="white",t.beginPath(),t.moveTo(i+n.stackheight/2,o),t.lineTo(i,o),t.lineTo(i,o+n.stackheight/2),t.lineTo(i+n.stackheight/2,o),t.closePath(),t.fill(),t.beginPath(),t.moveTo(i+n.stackheight/2,o+n.stackheight),t.lineTo(i,o+n.stackheight),t.lineTo(i,o+n.stackheight/2),t.lineTo(i+n.stackheight/2,o+n.stackheight),t.closePath(),t.fill())}}(t,e,r,i,n),e.rnext&&(i.to_qual||e.x2-e.x1>=20&&r.stackheight>=7&&(t.font=Math.min(12,Math.max(7,r.stackheight-4))+"pt Arial",t.fillStyle="white",t.fillText((o.nochr?"chr":"")+e.rnext,(e.x1+e.x2)/2,n+r.stackheight/2,e.x2-e.x1)))}function Nt(t,e,n,r){for(const[t,n]of e.regions.entries()){if(!n.to_printnt)continue;const e=new Set;for(const o of r)for(const r of o.segments){if(r.ridx!=t)continue;const o=r.boxes.filter((t=>"I"==t.opr));if(o.length)for(const t of o)e.add(n.x+n.scale(t.start))}}for(const n of r)for(const r of n.segments){const o=e.regions[r.ridx],i=r.boxes.filter((t=>"I"==t.opr));if(i.length){t.font=Math.max(12,e.stackheight-2)+"pt Arial";for(const s of i){const i=o.x+o.scale(s.start);s.qual?t.fillStyle=$(s.qual.reduce(((t,e)=>t+e),0)/s.qual.length/tt):t.fillStyle=z;const a=1==s.s.length?s.s:s.s.length;t.fillText(a,i,n.y+e.stackheight*(r.on2ndrow||0)+e.stackheight/2)}}}}async function St(t,e,n){const r=_t(t.qual),o=['<td style="color:black;text-align:left">Read</td>'];for(const e of t.boxes)for(let n=0;n<e.len;n++){t.seq[e.cidx+n];o.push('<td style="background:'+S(r[e.cidx+n]/tt)+'">'+t.seq[e.cidx+n]+"</td>")}const i=[];i.push('<li><span style="background:#6B4423;color:white">This segment in template is unmapped</span></li>'),1&t.flag&&i.push("<li>Template has multiple segments</li>"),2&t.flag&&i.push("<li>Each segment properly aligned</li>"),16&t.flag&&i.push("<li>Reverse complemented</li>"),32&t.flag&&i.push("<li>Next segment in the template is reverse complemented</li>"),64&t.flag&&i.push("<li>This is the first segment in the template</li>"),128&t.flag&&i.push("<li>This is the last segment in the template</li>"),256&t.flag&&i.push("<li>Secondary alignment</li>"),512&t.flag&&i.push("<li>Not passing filters</li>"),1024&t.flag&&i.push("<li>PCR or optical duplicate</li>"),2048&t.flag&&i.push("<li>Supplementary alignment</li>");let s={seq:t.seq,alignment:`<table style="border-spacing:0px;border-collapse:separate;text-align:center">\n\t\t\t <tr style="color:white">${o.join("")}</tr>\n\t\t\t</table>`,info:`<div style='margin-top:10px'>\n\t\t\t<span style="opacity:.5;font-size:.7em">TEMPLATE</span>: ${Math.abs(t.seq.length)} bp,\n\t\t\t<span style="opacity:.5;font-size:.7em">CIGAR</span>: ${t.cigarstr}\n\t\t\t<span style="opacity:.5;font-size:.7em">FLAG</span>: ${t.flag}\n\t\t\t<span style="opacity:.5;font-size:.7em">NAME: ${t.qname}</span>\n\t\t </div>\n\t\t <ul style='padding-left:15px'>${i.join("")}</ul>`};return t.discord_unmapped2&&(s.unmapped_mate=!0),s}async function At(t,e,n){const r=t.boxes[0].start,o=t.boxes[t.boxes.length-1],i=o.start+o.len,s=await vt(e,n.chr+":"+(r+1)+"-"+i),a=_t(t.qual),l=["<td>Reference</td>"],c=['<td style="color:black;text-align:left">Read</td>'];for(const e of t.boxes)if("H"!=e.opr)if("I"!=e.opr)if("D"!=e.opr&&"N"!=e.opr)if("S"!=e.opr)if("M"!=e.opr&&"="!=e.opr&&"X"!=e.opr&&"*"!=e.opr);else for(let n=0;n<e.len;n++){const o=s[e.start-r+n],i=t.seq[e.cidx+n];l.push("<td>"+o+"</td>"),"*"==t.qual?c.push('<td style="color:black;background:'+(o.toUpperCase()==i.toUpperCase()?S:E)+'">'+t.seq[e.cidx+n]+"</td>"):c.push('<td style="background:'+(o.toUpperCase()==i.toUpperCase()?S:E)(a[e.cidx+n]/tt)+'">'+t.seq[e.cidx+n]+"</td>")}else for(let n=0;n<e.len;n++)l.push("<td>"+s[e.start-r+n]+"</td>"),"*"==t.qual?c.push('<td style="background:'+P(1)+'">'+t.seq[e.cidx+n]+"</td>"):c.push('<td style="background:'+P(a[e.cidx+n]/tt)+'">'+t.seq[e.cidx+n]+"</td>");else if(e.len>=20)l.push('<td style="font-size:.8em;opacity:.5;white-space:nowrap">'+e.len+" bp</td>"),c.push('<td style="color:black;white-space:nowrap">-----------</td>');else for(let t=0;t<e.len;t++)l.push("<td>"+s[e.start-r+t]+"</td>"),c.push('<td style="color:black">-</td>');else for(let n=e.cidx;n<e.cidx+e.len;n++)l.push("<td>-</td>"),"*"==t.qual?c.push('<td style="color:#47FFFC;background:white">'+t.seq[n]+"</td>"):c.push('<td style="color:#47FFFC;background:'+S(a[n]/tt)+'">'+t.seq[n]+"</td>");let u=0,f=0,d=[],h=[],p=0;for(const e of t.boxes)u=f,f+=e.len,"S"==e.opr&&(p=1,d.push(u),h.push(f));const m=[];t.rnext&&m.push('<li>Next segment on <span style="background:#d48b37">'+(n.nochr?"chr":"")+t.rnext+", "+t.pnext+"</span></li>"),t.discord_wrong_insertsize&&t.discord_orientation?m.push('<li><span style="background:#3B7A57;color:white">Wrong insert size</span> mate position: '+t.pnext+'</li><li><span style="background:'+'#fc6df3;color:white">Segments also having wrong orientation</span> '+t.discord_orientation_direction+"</li>"):t.discord_wrong_insertsize?m.push('<li><span style="background:#3B7A57;color:white">Wrong insert size</span> mate position: '+t.pnext+"</li>"):t.discord_orientation?m.push('<li><span style="background:#fc6df3;color:white">Segments having wrong orientation</span> '+t.discord_orientation_direction+"</li>"):t.discord_unmapped2&&m.push('<li><span style="background:#6B4423;color:white">Other segment in template is unmapped</span></li>'),1&t.flag&&m.push("<li>Template has multiple segments</li>"),2&t.flag&&m.push("<li>Each segment properly aligned</li>"),16&t.flag&&m.push("<li>Reverse complemented</li>"),32&t.flag&&m.push("<li>Next segment in the template is reverse complemented</li>"),64&t.flag&&m.push("<li>This is the first segment in the template</li>"),128&t.flag&&m.push("<li>This is the last segment in the template</li>"),256&t.flag&&m.push("<li>Secondary alignment</li>"),512&t.flag&&m.push("<li>Not passing filters</li>"),1024&t.flag&&m.push("<li>PCR or optical duplicate</li>"),2048&t.flag&&m.push("<li>Supplementary alignment</li>");let g={seq:t.seq,alignment:`<table style="border-spacing:0px;border-collapse:separate;text-align:center;font-family:courier">\n\t\t\t <tr style="opacity:.6">${l.join("")}</tr>\n\t\t\t <tr style="color:white">${c.join("")}</tr>\n\t\t\t</table>`,info:`<div style='margin-top:10px'>\n\t\t\t<span style="opacity:.5;font-size:.7em">CHR</span>: ${n.chr.replace("chr","")},\n\t\t\t<span style="opacity:.5;font-size:.7em">START</span>: ${t.segstart_original+1},\n\t\t\t<span style="opacity:.5;font-size:.7em">STOP</span>: ${i},\n\t\t\t<span style="opacity:.5;font-size:.7em">READ LENGTH</span>: ${t.seq.length} bp,\n\t\t\t<span style="opacity:.5;font-size:.7em">TEMPLATE LENGTH</span>: ${Math.abs(t.tlen)} bp,\n\t\t\t<span style="opacity:.5;font-size:.7em">CIGAR</span>: ${t.cigarstr}\n\t\t\t<span style="opacity:.5;font-size:.7em">FLAG</span>: ${t.flag}\n\t\t\t<span style="opacity:.5;font-size:.7em">NAME: ${t.qname}</span>\n\t\t </div>\n\t\t <ul style='padding-left:15px'>${m.join("")}</ul>`,start_readpos:r+1,boxes:t.boxes,readpanel_DN_maxlength:20};return 1==p&&(g.soft_starts=d,g.soft_stops=h),t.discord_unmapped2&&(g.unmapped_mate=!0),g}function Mt(t){const e=i.createHmac("md5",it),n=[t.get("X-Auth-Token")||t.cookies.sessionid,t.query.gdcFileUUID,t.query.gdcFilePosition];return e.update(n.join("")).digest("hex")+".bam"}async function Tt(t){const e=t.query.regions;if(!Array.isArray(e)||0==e.length)throw"req.query.regions[] not non-empty array";const n=[];for(const r of e){const e=await Ct(r.chr,r.start,r.stop,t.get("X-Auth-Token"),t.query.gdcFileUUID,Mt(t),t.cookies.sessionid);n.push({filesize:e})}return n}async function Ct(t,e,n,r,o,i,s){const f={compression:!1};s?f.Cookie=`sessionid=${s}`:f["X-Auth-Token"]=r;const h=c.join(x.cachedir_bam,i),p=ot+"/slicing/view/"+o+"?region="+t+":"+e+"-"+n;try{if(await d.file_not_exist(h)&&(await l(a.stream(p,{method:"GET",headers:f}),u.createWriteStream(h)),await d.file_not_exist(h)))throw"BAM file slice is not found after downloading";const t=h+".bai";if(await d.file_not_exist(t)&&(await async function(t){await d.get_lines_bigfile({isbam:!0,args:["index",t],callback:()=>{}})}(h),await d.file_not_exist(t)))throw"index file is missing after indexing";const e=await u.promises.stat(h);return _(e.size,!0)}catch(t){throw t.stack&&console.log(t.stack),"Error with BAM slicing: "+(t.message||t)}}t.exports=t=>async(e,n)=>{try{if(delete e.query.isFileSlice,e.query.gdcFileUUID){const t=e.cookies.sessionid,n=e.get("X-Auth-Token");if(!n&&!t)throw"GDC token or sessionid missing";await w(e.query.gdcFileUUID,n,t),e.query.file=Mt(e),e.query.isFileSlice=!0}if(e.query.downloadgdc)return void n.send(await Tt(e));if(e.query.clientdownloadgdcslice){if(!e.query.file||!e.query.isFileSlice)throw"invalid query";const t=c.join(x.cachedir_bam,e.query.file),r=await u.promises.readFile(t);return n.writeHead(200,{"Content-Type":"application/octet-stream","Content-Disposition":"attachment; filename=gdc.bam","Content-Length":r.length}),void n.end(Buffer.from(r,"binary"))}if(!e.query.genome)throw".genome missing";const o=t[e.query.genome];if(!o)throw"invalid genome";if(e.query.getread)return void n.send(await async function(t,e){if(!e.query.chr)throw".chr missing";if(!e.query.qname)throw".qname missing";if(e.query.qname=decodeURIComponent(e.query.qname),!e.query.start)throw".start missing";if(!e.query.stop)throw".stop missing";const n={chr:e.query.chr,start:Number(e.query.start),stop:Number(e.query.stop),scale:()=>{},ntwidth:10};if(!Number.isInteger(n.start))throw".start not integer";if(!Number.isInteger(n.stop))throw".stop not integer";const o=await async function(t,e){let n,o,i,s,a,l,u,f,p;if(t.query.isFileSlice)a=c.join(x.cachedir_bam,t.query.file),await lt(t,a);else{if([s,a,l]=r.fileurl(t),s)throw s;i=l?await d.cache_index(a,t.query.indexURL||a+".bai"):null}if(t.query.unknownorder&&(u=Number(t.query.readstart),f=Number(t.query.readstop),Number.isNaN(u)||Number.isNaN(f)))throw"readstart/stop not provided for read with unknown order";if(await d.get_lines_bigfile({isbam:!0,args:["view",a,(t.query.nochr?t.query.chr.replace("chr",""):t.query.chr)+":"+e.start+"-"+e.stop],dir:i,callback:(r,i)=>{if(r.split("\t")[0]!=t.query.qname)return;const s=mt({sam_info:r,keepallboxes:!0,keepmatepos:!0,keepunmappedread:!0},e);if(s&&(!t.query.show_unmapped||!s.discord_unmapped2))if(t.query.show_unmapped&&t.query.getfirst){if(s.islast)return i.kill(),void(p=[s])}else if(t.query.show_unmapped&&t.query.getlast){if(s.isfirst)return i.kill(),void(p=[s])}else if(t.query.getfirst){if(s.isfirst)return i.kill(),void(p=[s])}else if(t.query.getlast){if(s.islast)return i.kill(),void(p=[s])}else if(t.query.unknownorder){if(s.segstart==u&&s.segstop==f)return i.kill(),void(p=[s])}else if(s.isfirst?n=s:s.islast&&(o=s),n&&o)return i.kill(),void(p=[n,o])}}),p){if(t.query.altseqs){const e={query_seq:p[0].seq,refseqs:t.query.refseqs,altseqs:t.query.altseqs,cigar_seq:p[0].cigarstr,start_position:p[0].segstart,ref_positions:t.query.ref_positions,refalleles:t.query.refalleles,altalleles:t.query.altalleles},n=(await h("align",JSON.stringify(e))).split("\n");let r;for(let t of n)t.includes("Final_output:")?r=JSON.parse(t.replace("Final_output:","")):console.log(t);p.alignments=r}return p}p=[],n&&p.push(n);o&&p.push(o);return p.length?p:null}(e,n);if(!o){if(e.query.show_unmapped)throw"mate not found";throw"read not found"}const i=[];for(const n of o)n.discord_unmapped1?i.push(await St(n,t,e.query)):i.push(await At(n,t,e.query));o.alignments&&(i[0].alignments=o.alignments);return{lst:i}}(o,e));const i=x.debugmode?new Date:null,s=await async function(t,e){let n;if(e.query.isFileSlice)n={genome:t,file:c.join(x.cachedir_bam,e.query.file),asPaired:e.query.asPaired,getcolorscale:e.query.getcolorscale,devicePixelRatio:e.query.devicePixelRatio?Number(e.query.devicePixelRatio):1},await lt(e,n.file);else{const[o,i,s]=r.fileurl(e);if(o)throw o;n={genome:t,file:i,asPaired:e.query.asPaired,getcolorscale:e.query.getcolorscale,devicePixelRatio:e.query.devicePixelRatio?Number(e.query.devicePixelRatio):1},s&&(n.dir=await d.cache_index(i,e.query.indexURL||i+".bai"))}if(e.query.pileupheight&&(n.pileupheight=Number(e.query.pileupheight),Number.isNaN(n.pileupheight)))throw".pileupheight is not integer";e.query.drop_pcrduplicates&&(n.drop_pcrduplicates=!0);if(e.query.variant){n.diff_score_plotwidth=Number(e.query.diff_score_plotwidth),e.query.max_diff_score&&(n.max_diff_score=Number(e.query.max_diff_score),n.min_diff_score=Number(e.query.min_diff_score));const t=e.query.variant.split(".");if(n.strictness=e.query.strictness,!Number.isInteger(t.length%4))throw"invalid variant, not chr.pos.ref.alt";n.alleleAlreadyUpdated=e.query.alleleAlreadyUpdated,n.alleleAlreadyUpdated&&(n.altseqs=e.query.altseqs,n.refseqs=e.query.refseqs,n.altalleles=e.query.altalleles,n.refalleles=e.query.refalleles,n.leftflankseqs=e.query.leftflankseqs,n.rightflankseqs=e.query.rightflankseqs,n.ref_positions=e.query.ref_positions);const r=t.length/4,o=[];for(let e=0;e<r;e++)o.push({chr:t[4*e],pos:Number(t[4*e+1]),ref:t[4*e+2],alt:t[4*e+3]});if(n.variant=o,e.query.alignOneGroup&&(n.alignOneGroup=e.query.alignOneGroup),Number.isNaN(n.variant.pos))throw"variant pos not integer"}else if(e.query.sv){const t=e.query.sv.split(".");if(t.length<6)throw"invalid sv, not chrA.posA.chrB.posB";if(n.sv={chrA:t[0],startA:Number(t[1]),strandA:Number(t[2]),chrB:t[3],startB:Number(t[4]),strandB:Number(t[5])},Number.isNaN(n.sv.startA))throw"sv.startA not integer";if(Number.isNaN(n.sv.startB))throw"sv.startB not integer"}if(Number.isFinite(Number(e.query.stackstart))){if(!e.query.stackstop)throw".stackstop missing";if(n.partstack={start:Number(e.query.stackstart),stop:Number(e.query.stackstop)},Number.isNaN(n.partstack.start))throw".stackstart not integer";if(Number.isNaN(n.partstack.stop))throw".stackstop not integer";if(!e.query.grouptype)throw".grouptype required for partstack";n.grouptype=e.query.grouptype}e.query.gdc||(e.query.nochr?n.nochr="string"==typeof e.query.nochr?JSON.parse(e.query.nochr):e.query.nochr:n.nochr=await d.bam_ifnochr(n.file,t,n.dir));if(n.regions=e.query.regions,!Array.isArray(n.regions)||0==n.regions.length)throw"q.regions[] not non-empty array";let o=0;for(const t of n.regions){if(!t.chr)throw".chr missing from a region";if(!Number.isInteger(t.start))throw".start not integer of a region";if(!Number.isInteger(t.stop))throw".stop not integer of a region";t.scale=e=>Math.ceil(t.width*(e-t.start)/(t.stop-t.start)),t.ntwidth=t.width/(t.stop-t.start),o=Math.max(o,t.ntwidth)}return n.stacksegspacing=Math.max(2,5*o),n.readcount_skipped=0,n}(o,e);n.send(await async function(t){await async function(t){if(t.variant){let e=0,n=0,r=0,o=t.variant[0].pos,i=t.variant[0].pos+Math.max(t.variant[0].ref.length,t.variant[0].alt.length);for(const s of t.variant){const t=Math.abs(s.pos-Math.max(s.ref.length,s.alt.length));t>e&&(e=t,n=r),o>s.pos&&(o=s.pos),i<s.pos+Math.max(s.ref.length,s.alt.length)&&(i=s.pos+Math.max(s.ref.length,s.alt.length)),r+=1}e=Math.floor(1.5*Math.max(t.variant[n].ref.length,t.variant[n].alt.length));const s={chr:t.variant[0].chr,start:o-e,stop:i+e};return await ut(t,[s]),await ft(s,t),void(t.regions[0].lines=s.lines)}await ut(t,t.regions);for(const e of t.regions)await ft(e,t)}(t),t.totalnumreads=t.regions.reduce(((t,e)=>t+e.lines.length),0);const e={nochr:t.nochr,count:{r:t.totalnumreads},groups:[]};t.read_limit_reached&&(e.count.read_limit_reached=t.read_limit_reached);t.canvaswidth=t.regions[t.regions.length-1].x+t.regions[t.regions.length-1].width;{const n=await async function(t){const e=[],n=[];let r=0;for(const o of t.regions){for(const t of o.lines)e.push({sam_info:t,tempscore:""});r=o.x+o.width,n.push(r)}if(0==e.length)return{groups:[{type:v.type_all,regions:v.duplicateRegions(t.regions),templates:e,messages:[],partstack:t.partstack,widths:n}]};if(t.variant){if(1==t.regions.length)return await y(t,e,n);console.log("Indel pipeline works only in single region. Please check!")}if(t.sv&&t.regions.length>1)return async function(t,e,n){const r=v.make_type2group(e),o=[];for(let t=0;t<e.regions.length;t++){const n=e.regions[t],r=(await d.get_fasta(e.genome,n.chr+":"+n.start+"-"+n.stop)).split("\n").slice(1).join("").toUpperCase(),i=[];for(const e of n.lines)i.push({sam_info:e,tempscore:"",ridx:t});const s={refseq:r,start:n.start,stop:n.stop,entries:i};0==t?(s.chr=e.sv.chrA,s.pos=e.sv.startA):1==t?(s.chr=e.sv.chrB,s.pos=e.sv.startB):console.log("More than two regions, please check"),o.push(s)}const i=new Date,s=(await h("sv",JSON.stringify(o))).split("\n"),a=new Date;let l,c;console.log("Time taken to run rust SV pipeline:",a-i,"ms");for(let t of s)t.includes("multi_region_templates:")?l=JSON.parse(t.replace("multi_region_templates:","")):t.includes("single_region_templates:")&&(c=JSON.parse(t.replace("single_region_templates:","")));if(!e.grouptype||"support_sv"==e.grouptype)for(const t of l)r[v.type_supportsv].templates.push(t);if(!e.grouptype||"support_ref"==e.grouptype)for(const t of c)r[v.type_supportref].templates.push(t);const u=[];for(const t in r){const e=r[t];0!=e.templates.length&&(t==v.type_supportsv?1==e.templates.length?e.messages.push({isheader:!0,t:e.templates.length+" read supporting SV/fusion"}):e.messages.push({isheader:!0,t:e.templates.length+" reads supporting SV/fusion"}):t==v.type_supportref&&e.messages.push({isheader:!0,t:e.templates.length+" reads supporting reference allele"}),e.widths=n,u.push(e))}return{groups:u}}(0,t,n);return{groups:[{type:v.type_all,regions:v.duplicateRegions(t.regions),templates:e,messages:[],partstack:t.partstack,widths:n}]}}(t);t.groups=n.groups,t.variant&&(e.ref_alleles=n.refalleles,e.alt_alleles=n.altalleles,e.allele_positions=n.ref_positions,e.strand_probability=n.strand_probability,e.alternate_forward_count=n.alternate_forward_count,e.reference_forward_count=n.reference_forward_count,e.alternate_reverse_count=n.alternate_reverse_count,e.reference_reverse_count=n.reference_reverse_count,1==n.strand_significance&&(e.strand_significance=!0),t.alleleAlreadyUpdated||(e.refseqs=n.refseqs,e.altseqs=n.altseqs,e.leftflankseqs=n.leftflankseqs,e.rightflankseqs=n.rightflankseqs,e.ref_positions=n.ref_positions,e.refalleles=n.refalleles,e.altalleles=n.altalleles)),Number.isFinite(t.max_diff_score)&&t.variant?(e.max_diff_score=t.max_diff_score,e.min_diff_score=t.min_diff_score):Number.isFinite(n.max_diff_score)&&(e.max_diff_score=n.max_diff_score,e.min_diff_score=n.min_diff_score),n.refalleleerror&&(e.refalleleerror=n.refalleleerror)}if(0==e.count.r)throw"No reads in view range.";if(t.alignOneGroup){const e=t.groups.find((e=>e.type==t.alignOneGroup));if(!e)throw"cannot find group for realignment";let n=pt(t,e);return n=yt(e,t,n),await async function(t,e,n){let r;if(e.variant)if("support_ref"==t.type){let o=e.leftflankseqs[0].length;r=t.partstack?await ct(n,o,t.partstack.start,t.partstack.stop,e.refseqs[0]):await ct(n,o,0,0,e.refseqs[0])}else if("support_no"==t.type){let o=e.leftflankseqs[0].length;r=t.partstack?await ct(n,o,t.partstack.start,t.partstack.stop):await ct(n,o)}else if("support_amb"==t.type)console.log("Realignment of reads in ambiguous group is not currently implemented");else if(t.type.includes("support_alt")){for(let o=0;o<e.variant.length;o++)if(t.type=="support_alt"+o.toString()){let i=e.leftflankseqs[o].length;r=t.partstack?await ct(n,i,t.partstack.start,t.partstack.stop,e.altseqs[o]):await ct(n,i,0,0,e.altseqs[o])}}else console.log("Unaccounted group, please check");return{alignmentData:r}}(e,t,n)}let n=[];for(const r of t.groups){let o=pt(t,r);o=yt(r,t,o),await gt(r,t,o),await ht(o,t),bt(r,o,t);const i={type:r.type,width:t.canvaswidth,height:r.canvasheight,stackheight:r.stackheight,stackcount:r.stacks.length,allowpartstack:r.allowpartstack,templatebox:r.returntemplatebox,count:{r:o.reduce(((t,e)=>t+e.segments.length),0)}},s=p(t.canvaswidth*t.devicePixelRatio,r.canvasheight*t.devicePixelRatio),a=s.getContext("2d");t.devicePixelRatio>1&&a.scale(t.devicePixelRatio,t.devicePixelRatio),a.textAlign="center",a.textBaseline="middle",i.messages=r.messages,i.messagerowheights=0;for(const e of o)kt(a,e,r,t);Nt(a,r,t,o),t.asPaired&&(i.count.t=o.length),t.variant&&(i.diff_scores_img=await st(t,r,o,e.max_diff_score,e.min_diff_score),"support_alt0"==i.type?i.group_color=W:"support_alt1"==i.type?i.group_color=J:"support_alt2"==i.type?i.group_color=V:"support_alt3"==i.type?i.group_color=Y:"support_alt4"==i.type?i.group_color=Q:"support_alt5"==i.type?i.group_color=K:"support_ref"==i.type&&(i.group_color=X)),i.src=s.toDataURL(),e.groups.push(i),n=[...n,...o]}t.readcount_skipped&&(e.count.skipped=t.readcount_skipped);t.getcolorscale&&(e.colorscale=function(t){const e=160,n=20,r=1,o=12,i=5,s=100,a=4,l=s+e+10,c=2*o+i+a+4*(n+r),u=p(t.devicePixelRatio*l,t.devicePixelRatio*c),f=u.getContext("2d");t.devicePixelRatio>1&&f.scale(t.devicePixelRatio,t.devicePixelRatio);f.fillStyle="black",f.font=o+"pt Arial",f.textAlign="center",f.fillText("Base quality",s+e/2,o);let d=2*o+i;function h(t,r,o){const i=s,a=f.createLinearGradient(i,o,i+e,o);a.addColorStop(0,r),a.addColorStop(1,t),f.fillStyle=a,f.fillRect(i,o,e,n)}return f.strokeStyle="black",f.beginPath(),f.moveTo(s,d),f.lineTo(s,d+a),f.moveTo(s+e/4,d),f.lineTo(s+e/4,d+a),f.moveTo(s+e/2,d),f.lineTo(s+e/2,d+a),f.moveTo(s+3*e/4,d),f.lineTo(s+3*e/4,d+a),f.moveTo(s+e,d),f.lineTo(s+e,d+a),f.closePath(),f.stroke(),f.fillText(40,s,d),f.fillText(30,s+e/4,d),f.fillText(20,s+e/2,d),f.fillText(10,s+3*e/4,d),f.fillText(0,s+e,d),f.textAlign="left",f.textBaseline="middle",d+=a,f.fillText("Match",0,d+n/2),h(N,q,d),d+=n+r,f.fillStyle="black",f.fillText("Mismatch",0,d+n/2),h(O,j,d),d+=n+r,f.fillStyle="black",f.fillText("Softclip",0,d+n/2),h(I,R,d),d+=n+r,f.fillStyle="black",f.fillText("Insertion",0,d+n/2),h(Z,z,d),{width:l,height:c,src:u.toDataURL()}}(t));if(!t.partstack)if(0==e.count.r);else{if(!t.pileupheight)throw"pileupheight missing";e.pileup_data=await async function(t,e){const n=p(t.canvaswidth*t.devicePixelRatio,t.pileupheight*t.devicePixelRatio),r=n.getContext("2d");t.devicePixelRatio>1&&r.scale(t.devicePixelRatio,t.devicePixelRatio);const o=[];let i=0;for(const[n,r]of t.regions.entries()){o[n]=await dt(t,r),at(n,r,e,o[n]);for(const t of o[n])t&&(i=Math.max(i,t.total))}for(const[e,n]of t.regions.entries()){const s=t.pileupheight/i;for(const i of o[e]){if(!i)continue;const e=(i.position-n.start)*n.ntwidth+n.x,o=n.ntwidth>=1?e:Math.floor(e),a=Math.max(1,n.ntwidth);{r.fillStyle=H;const e=i.total*s;r.fillRect(o,t.pileupheight-e,a,e)}let l=0;if(i.A){r.fillStyle=b.A;const e=i.A*s;r.fillRect(o,t.pileupheight-l-e,a,e),l+=e}if(i.C){r.fillStyle=b.C;const e=i.C*s;r.fillRect(o,t.pileupheight-l-e,a,e),l+=e}if(i.G){r.fillStyle=b.G;const e=i.G*s;r.fillRect(o,t.pileupheight-l-e,a,e),l+=e}if(i.T){r.fillStyle=b.T;const e=i.T*s;r.fillRect(o,t.pileupheight-l-e,a,e),l+=e}if(i.softclip){r.fillStyle=R;const e=i.softclip*s;r.fillRect(o,t.pileupheight-l-e,a,e)}}}return{width:t.canvaswidth,maxValue:i,src:n.toDataURL()}}(t,n)}return e}(s)),x.debugmode&&console.log("bam.js time ms",new Date-i)}catch(t){n.send({error:t.message||t}),t.stack&&console.log(t.stack)}}},8953:(t,e,n)=>{"use strict";n.d(e,{Y:()=>s});n(8171).jStat,n(1017),n(9699).features;const r=n(3856),o=n(1271).run_rust,i=(n(2081).spawn,n(2781).Readable,n(4521),n(2384));n(7147),n(334).clustalo;async function s(t,e,n){const s=t.regions[0].lines[0].split("\t")[9].length;let a=!1,l=[],c=[],u=[],f=[],d=[],h=[],p=[];if(t.alleleAlreadyUpdated)l=t.leftflankseqs,c=t.rightflankseqs,h=t.refseqs,p=t.altseqs,u=t.refalleles,f=t.altalleles,d=t.ref_positions,0!=h[0].toUpperCase().localeCompare((l[0]+u[0]+c[0]).toUpperCase())&&(console.log("Reference allele is not correct for variant 0"),a=!0);else{let e,n,o=0;for(const i of t.variant){let a="",l="";if(!(0!=i.ref.length&&"-"!=i.ref||"-"!=i.alt&&0!=i.alt.length))throw"Both Ref and Alt alleles are missing";if(0==i.ref.length||"-"==i.ref)a=(await r.get_fasta(t.genome,i.chr+":"+i.pos+"-"+i.pos)).split("\n").slice(1).join("").toUpperCase(),l=a+i.alt,i.pos-=1;else if("-"==i.alt||0==i.alt.length){const e=(await r.get_fasta(t.genome,i.chr+":"+i.pos+"-"+i.pos)).split("\n").slice(1).join("").toUpperCase();a=e+i.ref,l=e,i.pos-=1}else l=i.alt,a=i.ref;const c=i.pos,h=a.toUpperCase(),p=l.toUpperCase();0==o?(e=c-s,n=c+a.length+1+s):(c-s<e&&(e=c-s),c+a.length+1+s>n&&(n=c+a.length+1+s)),u.push(h),f.push(p),d.push(c),o+=1}o=0;for(const i of t.variant){const s=(await r.get_fasta(t.genome,i.chr+":"+e+"-"+d[o])).split("\n").slice(1).join("").toUpperCase(),a=(await r.get_fasta(t.genome,i.chr+":"+(d[o]+u[o].length+1)+"-"+n)).split("\n").slice(1).join("").toUpperCase(),m=s+u[o]+a,g=s+f[o]+a;console.log(i.chr+"."+d[o]+"."+u[o]+"."+f[o]),o+=1,l.push(s),c.push(a),h.push(m),p.push(g)}}const m=[];for(let t=0;t<e.length;t++){const n=e[t].sam_info.split("\t");m.push({read_sequence:n[9],start_position:Number(n[3]),cigar:n[5],flag:Number(n[1])})}const g=[];for(let t=0;t<u.length;t++)g.push({ref_position:Number(d[t]),refallele:u[t],altallele:f[t],refseq:h[t],altseq:p[t],leftflankseq:l[t],rightflankseq:c[t]});Number.isFinite(Number(t.strictness))||(t.strictness=1);const y={reads:m,alleles:g,strictness:Number(t.strictness)},v=new Date,b=await o("indel",JSON.stringify(y)),_=new Date;console.log("Time taken to run rust indel pipeline:",_-v,"ms");const w=b.split("\n");let x,k,q,N,S,A,M=0;for(let t of w)t.includes("Final_output:")?x=JSON.parse(JSON.parse(t.replace("Final_output:",""))):1==u.length&&t.includes("fisher_strand:")?(k=JSON.parse(t.replace("fisher_strand:","")),q=k.alternate_forward_count,N=k.alternate_reverse_count,S=k.reference_forward_count,A=k.reference_reverse_count,M=k.p_value):console.log(t);let T=!1;1==t.variant.length&&M>60&&(T=!0);const C=i.make_type2group(t);t.variant.length;let j=1;for(let n=0;n<x.length;n++){const r=x[n],o=r.read_number,s=r.categories,a=r.categories[0],l=[];if(s.length>1){for(let t=1;t<s.length;t++)l.push(s[t]);s.length-1>j&&(j=s.length-1)}if(a.includes("alt"))for(let n=0;n<t.variant.length;n++)a=="alt"+n.toString()&&C[i.type_supportalt+n.toString()]&&(e[o].tempscore=["alt"+n.toString()],C[i.type_supportalt+n.toString()].templates.push(e[o]));else"ref"==a?C[i.type_supportref]&&(e[o].tempscore=["ref"],C[i.type_supportref].templates.push(e[o])):"none"==a?C[i.type_supportno]&&(e[o].tempscore=l,C[i.type_supportno].templates.push(e[o])):"amb"==a?C[i.type_supportamb]&&(e[o].tempscore=l,C[i.type_supportamb].templates.push(e[o])):console.log("Unaccounted group, please check")}const O=[];for(const e in C){const r=C[e];if(0!=r.templates.length){if(e.includes(i.type_supportalt))for(let n=0;n<t.variant.length;n++)e==i.type_supportalt+n.toString()&&(1==t.variant.length?1==r.templates.length?r.messages.push({isheader:!0,t:r.templates.length+" read supporting the alternative allele"}):r.messages.push({isheader:!0,t:r.templates.length+" reads supporting the alternative allele"}):1==r.templates.length?r.messages.push({isheader:!0,t:r.templates.length+" read support the alternative allele with "+f[n]+" sequence"}):r.messages.push({isheader:!0,t:r.templates.length+" reads support the alternative allele with "+f[n]+" sequence"}));else e==i.type_supportamb?1==r.templates.length?r.messages.push({isheader:!0,t:r.templates.length+" ambiguous read"}):r.messages.push({isheader:!0,t:r.templates.length+" ambiguous reads"}):e==i.type_supportref?1==r.templates.length?r.messages.push({isheader:!0,t:r.templates.length+" read supporting the reference allele"}):r.messages.push({isheader:!0,t:r.templates.length+" reads supporting the reference allele"}):e==i.type_supportno?1==r.templates.length?r.messages.push({isheader:!0,t:r.templates.length+" read supporting neither reference nor alternative alleles"}):r.messages.push({isheader:!0,t:r.templates.length+" reads supporting neither reference nor alternative alleles"}):console.log("Unaccounted group, please check");r.widths=n,O.push(r)}}const E=[];for(let t=0;t<O.length;t++)O[t].type.includes("support_alt")&&E.push(O[t]);for(let t=0;t<O.length;t++)"support_ref"==O[t].type&&E.push(O[t]);for(let t=0;t<O.length;t++)"support_no"==O[t].type&&E.push(O[t]);for(let t=0;t<O.length;t++)"support_amb"==O[t].type&&E.push(O[t]);return{groups:E,refalleleerror:a,ref_positions:d,refalleles:u,altalleles:f,max_diff_score:j,min_diff_score:0,strand_probability:M,strand_significance:T,refseqs:h,altseqs:p,leftflankseqs:l,rightflankseqs:c,alternate_forward_count:q,alternate_reverse_count:N,reference_forward_count:S,reference_reverse_count:A}}},1270:(t,e,n)=>{const r=n(9699),o=n(3856),i=n(6718).createCanvas,s=n(2273).basecolor;t.exports=async(t,e)=>{try{const[n,a,l]=r.fileurl(t);if(n)throw n;let c=t.query.usegrade;const 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e=0;e<c;e++)t.beginPath(),u?(t.moveTo(f,r),t.lineTo(f+a,r+i/2),t.moveTo(f+a,r+i/2+1),t.lineTo(f,r+i)):(t.moveTo(f+a,r),t.lineTo(f,r+i/2),t.moveTo(f,r+i/2+1),t.lineTo(f+a,r+i)),t.stroke(),f+=a+l}t.exports=t=>async(e,n)=>{try{n.send(await async function(t,e){const[n,m,g]=r.fileurl(t);if(n)throw n;let y,v,b,_,w;if(t.query.fileIsBigbed=await o.testIfFileIsBigbed(m),t.query.getdata)t.query.getBED;else{if(y=Number(t.query.stackheight),v=Number(t.query.stackspace),b=Number(t.query.regionspace),_=Number(t.query.width),Number.isNaN(y))throw"stackheight is not integer";if(w=Math.max(10,y-2),Number.isNaN(v))throw"stackspace is not integer";if(Number.isNaN(b))throw"regionspace is not integer";if(Number.isNaN(_))throw"width is not a number"}if(t.query.usevalue){if(!t.query.usevalue.key)throw".key missing from 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j){const i=S&&n.category&&S[n.category]?S[n.category].color:n.color||x;r.fillStyle=i;for(const i of n.rglst){let s=0;for(let e=0;e<i.idx;e++)s+=t.query.rglst[e].width+b;const a=t.query.rglst[i.idx],l=[];n.utr5&&l.push(...n.utr5),n.utr3&&l.push(...n.utr3),!n.exon||n.coding&&0!=n.coding.length||l.push(...n.exon);for(const t of l){const e=Math.max(a.start,t[0]),i=Math.min(a.stop,t[1]),l=s+a.scale(a.reverse?i:e),c=s+a.scale(a.reverse?e:i);r.fillRect(l,O,Math.max(1,c-l),y-2*O),h(o,l,c,1,n)}const c=[];n.exon?n.coding&&n.coding.length>0&&c.push(...n.coding):c.push([n.start,n.stop]);for(const t of c){const i=Math.max(a.start,t[0]),l=Math.min(a.stop,t[1]),c=s+a.scale(a.reverse?l:i),u=s+a.scale(a.reverse?i:l);r.fillRect(c,0,Math.max(1,u-c),y),h(o,c,u,1,n),n.strand&&e&&(r.strokeStyle="white",p(r,n.strand,c,O,u-c,y-2*O))}}}return{src:n.toDataURL(),height:y,mapisoform:o}}if(t.query.hideItemNames)for(const t of j)delete t.name;let E=null;if(A&&j.length<50){E=[];for(const t of j){const e={};for(const 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n=D.measureText(t).width;e.canvas.namewidth=n,$?e.canvas.start>=n+1?(e.canvas.namestart=e.canvas.start-1,o=e.canvas.namestart-n,e.canvas.textalign="right"):e.canvas.stop+n+1<=_?(e.canvas.namestart=e.canvas.stop+1,i=e.canvas.namestart+n,e.canvas.textalign="left"):n>e.canvas.stop-e.canvas.start?e.canvas.start>_-e.canvas.stop?(e.canvas.namestart=e.canvas.start-1,o=e.canvas.namestart-n,e.canvas.textalign="right"):(e.canvas.namestart=e.canvas.stop+1,i=e.canvas.namestart+n,e.canvas.textalign="left"):(e.canvas.namehover=!0,e.canvas.textalign="left"):Math.min(_,e.canvas.stop)-Math.max(0,e.canvas.start)>=n+20?e.canvas.namein=!0:e.canvas.start>=n+1?(e.canvas.namestart=e.canvas.start-1,o=e.canvas.namestart-n,e.canvas.textalign="right"):e.canvas.stop+n+1<=_?(e.canvas.namestart=e.canvas.stop+1,i=e.canvas.namestart+n,e.canvas.textalign="left"):e.canvas.namein=!0}}e.canvas.stop-e.canvas.start>.3*_&&(H=[]);for(let 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t.selectCohort.term.id)throw"termdb.selectCohort.term.id is not string";if("categorical"!=t.selectCohort.term.type)throw'type is not hardcoded "categorical" from termdb.selectCohort.term';if(!t.selectCohort.values)throw"values[] missing from termdb.selectCohort";if(!Array.isArray(t.selectCohort.values))throw"termdb.selectCohort.values is not array";if(0==t.selectCohort.values.length)throw"termdb.selectCohort.values[] cannot be empty";for(const e of t.selectCohort.values){if(!e.keys)throw"keys[] missing from one of selectCohort.values[]";if(!Array.isArray(e.keys))throw"keys[] is not array from one of selectCohort.values[]";if(0==e.keys.length)throw"keys[] is empty from one of selectCohort.values[]"}}if(t.restrictAncestries){if(!Array.isArray(t.restrictAncestries)||0==t.restrictAncestries.length)throw"termdb.restrictAncestries[] is not non-empty array";for(const e of t.restrictAncestries){if(!e.name)throw"name missing from one of restrictAncestries";if("object"!=typeof e.tvs)throw".tvs{} 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n}}(t);const{mayGetGeneVariantData:f,getTermTypes:d,mayGetMatchingGeneNames:p}=n(7833);t.mayGetGeneVariantData=f,t.getTermTypes=d,t.mayGetMatchingGeneNames=p,null!==(c=t.cohort)&&void 0!==c&&null!==(u=c.db)&&void 0!==u&&u.refresh&&e&&l(t,e,s)}async function f(t,e){if(!t.track)throw"no mds2 track; missing ds.track{}";const n=t.track;n.name||(n.name=t.label),function(t){if(!t.populations)return;if(!Array.isArray(t.populations))throw"populations should be array";for(const e of t.populations){if(!e.key)throw"key missing from a population";if(e.label||(e.label=e.key),!Array.isArray(e.sets))throw".sets is not an array in population: "+e.key;for(const t of e.sets){if(!t.infokey_AC)throw"infokey_AC missing from a set of population: "+e.key;if(!t.infokey_AN)throw"infokey_AN missing from a set of population: "+e.key;if(e.termfilter&&!t.termfilter_value)throw"termfilter_value missing from a set of population where termfilter is set: "+e.key}}}(n),await async function(t,e,n){if(!t)return;if(!t.chr2bcffile)throw"vcftk.chr2bcffile is missing";{if("object"!=typeof t.chr2bcffile)throw"chr2bcffile not an object";for(const e in t.chr2bcffile)t.chr2bcffile[e]=r.join(a.tpmasterdir,t.chr2bcffile[e]);const n={file:t.chr2bcffile[e.defaultcoord.chr]};if(!n.file)throw"default chr missing from chr2bcffile";await o.init_one_vcf(n,e,!0),t.info=n.info,t.format=n.format,t.samples=n.samples,t.nochr=n.nochr}if(t.AD&&t.AD.chr2bcffile){if("object"!=typeof t.AD.chr2bcffile)throw"AD.chr2bcffile not an object";for(const e in t.AD.chr2bcffile)t.AD.chr2bcffile[e]=r.join(a.tpmasterdir,t.AD.chr2bcffile[e]);const i={file:t.AD.chr2bcffile[e.defaultcoord.chr]};if(!i.file)throw"default chr missing from AD.chr2bcffile";await o.init_one_vcf(i,e,!0),t.AD.info=i.info,t.AD.format=i.format,t.AD.samples=i.samples,t.AD.nochr=i.nochr,console.log(n.label+" vcf: AD: "+t.AD.samples.length+" samples");for(const e of t.AD.samples){const t=Number(e.name);if(!Number.isInteger(t))throw"non-integer vcf sample: "+e.name;e.name=t}}if(t.samples){for(const e of t.samples){const t=Number(e.name);if(!Number.isInteger(t))throw"non-integer vcf sample: "+e.name;e.name=t}console.log(n.label+" vcf: "+t.samples.length+" samples")}else console.log(n.label+" vcf: no samples");if(t.numerical_axis&&t.numerical_axis.info_keys){if(!Array.isArray(t.numerical_axis.info_keys))throw"numerical_axis.info_keys should be an array";for(const e of t.numerical_axis.info_keys){const n=t.info[e.key];if(!n)throw'INFO field "'+e.key+'" not found for numerical_axis';if("Float"!=n.Type&&"Integer"!=n.Type)throw'INFO field "'+e.key+'" from numerical_axis not of integer or float type';if("1"!=n.Number&&"A"!=n.Number)throw'for numerical axis, INFO field "'+e.key+'" only allows to be Number=1 or Number=A'}}if(t.plot_mafcov){if(!t.AD)throw".plot_mafcov enabled but .AD{} missing from vcf";if(!t.AD.samples)throw".plot_mafcov enabled but no samples from 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vcf";if(!t.format)throw".termdb_bygenotype enabled but no FORMAT fields from vcf";if(!t.format.GT)throw".termdb_bygenotype enabled but the GT FORMAT field is missing";if(!n.cohort)throw"termdb_bygenotype but ds.cohort missing";if(!n.cohort.termdb)throw"termdb_bygenotype but ds.cohort.termdb missing";if(t.termdb_bygenotype.getAF){if(!t.termdb_bygenotype.termid_sex)throw"termid_sex missing for getAF at termdb_bygenotype";if(!t.termdb_bygenotype.value_male)throw"value_male missing for getAF at termdb_bygenotype";const e=n.cohort.termdb.q.getSample2value(t.termdb_bygenotype.termid_sex);t.termdb_bygenotype.male_samples=new Set;for(const n of e)n.value==t.termdb_bygenotype.value_male&&t.termdb_bygenotype.male_samples.add(n.sample);if(!t.termdb_bygenotype.sex_chrs)throw"sex_chrs missing for getAF at termdb_bygenotype";if(!Array.isArray(t.termdb_bygenotype.sex_chrs))throw"sex_chrs is not array";t.termdb_bygenotype.sex_chrs=new Set(t.termdb_bygenotype.sex_chrs)}}if(t.samples){t.sample2arrayidx=new Map;for(const[e,n]of t.samples.entries())t.sample2arrayidx.set(n.name,e)}}(n.vcf,e,t),function(t){if(!t.info_fields)return;if(!Array.isArray(t.info_fields))throw"tk.info_fields is not array";for(const e of t.info_fields){if(!e.key)throw".key missing from one of tk.info_fields[]";if(t.vcf&&t.vcf.info&&!t.vcf.info[e.key])throw`info field ${e.key} missing from tk.vcf.info{}`;if(e.label||(e.label=e.key),e.iscategorical){if(!Array.isArray(e.values))throw".values[] not an array of categorical INFO field: "+e.key;for(const t of e.values){if(!t.key)throw"key missing from a value of categorical INFO: "+e.key;t.label||(t.label=t.key)}}else if(e.isfloat||e.isinteger){if(!e.range)throw".range{} missing from a numerical INFO: "+e.key;s(e.range,"tk.info_fields[]")}else if(!e.isflag)throw"tk.info_fields unknown type: "+e.key}}(n),await async function(t,e,n){if(!t)return;if(!Array.isArray(t.tracks))throw"ld.tracks[] not an 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t=e.term.id;t.startsWith("case.")&&(t="occurrence."+t),n.push(t)}return n.join(",")}function s(t){if(!t.gene&&"string"!=typeof t.gene)throw"p.gene does not provide non-empty string";const e={op:"and",content:[]};return t.gene&&e.content.push({op:"=",content:{field:"cnv.consequence.gene.symbol",value:t.gene.split(",")}}),t.filter0&&e.content.push(t.filter0),t.filterObj&&e.content.push(l("string"==typeof t.filterObj?JSON.parse(t.filterObj):t.filterObj)),e}t.queries.geneCnv.bygene.get=async t=>{var e;const a=x(t),l=await o.post(i.join(c,"cnv_occurrences"),{headers:a,body:JSON.stringify({size:1e5,fields:n(t),filters:s(t)})}),u=JSON.parse(l.body);if(!Array.isArray(null==u||null===(e=u.data)||void 0===e?void 0:e.hits))throw"geneCnv response body is not {data:hits[]}";const f={ssm_id:"geneCnvGain",dt:r.dtcnv,class:r.mclasscnvgain,samples:[]},d={ssm_id:"geneCnvLoss",dt:r.dtcnv,class:r.mclasscnvloss,samples:[]};for(const e of u.data.hits){if("object"!=typeof e.cnv)throw"hit.cnv{} not obj";if("object"!=typeof e.case)throw"hit.case{} not obj";if(!e.cnv.gene_level_cn)throw"hit.cnv.gene_level_cn is not true";let n;if("Gain"==e.cnv.cnv_change)n=f;else{if("Loss"!=e.cnv.cnv_change)throw"hit.cnv.cnv_change is not Gain/Loss";n=d}const r={sample_id:e.case.submitter_id};if(t.twLst)for(const n of t.twLst)k(r,e.case,n);r["case.case_id"]=e.case.case_id,n.samples.push(r)}const h=[];return f.samples.length&&h.push(f),d.samples.length&&h.push(d),h}}function w(t,e){if(!e)return;const n=e.split(",");for(const e of n){const n=e.split("--");if(2==n.length)return t.geneA=n[0].split("(")[0],void(t.geneB=n[1].split("(")[0])}}function x(t){const e={"Content-Type":"application/json",Accept:"application/json"};return t&&(t.token&&(e["X-Auth-Token"]=t.token),t.sessionid&&(e.Cookie="sessionid="+t.sessionid)),e}function k(t,e,n){const r=n.term.id.split(".");if(function e(o,i){const s=r[i];if(i==r.length-1)return void(t[n.term.id]?t[n.term.id].add(o[s]):t[n.term.id]=o[s]);const a=o[s];if(null==a)return;if(Array.isArray(a)){t[n.term.id]=new Set;for(const t of a)e(t,i+1);return}e(a,i+1)}(e,1),t[n.term.id]instanceof Set&&(t[n.term.id]=[...t[n.term.id]][0]),n.term.id in t)if("categorical"==n.term.type){const e=function(t,e){var n,r,o,i,s,a,l;if("custom-groupset"==(null===(n=e.q)||void 0===n?void 0:n.type)&&Array.isArray(null===(r=e.q)||void 0===r||null===(o=r.groupsetting)||void 0===o||null===(i=o.customset)||void 0===i?void 0:i.groups))for(const n of e.q.groupsetting.customset.groups){if(!Array.isArray(n.values))throw"group.values[] not array from tw.q.groupsetting.customset.groups";if(-1!=n.values.findIndex((e=>e.key==t)))return n.name}if("predefined-groupset"==(null===(s=e.q)||void 0===s?void 0:s.type)&&Number.isInteger(null===(a=e.q.groupsetting)||void 0===a?void 0:a.predefined_groupset_idx)&&null!==(l=e.term.groupsetting)&&void 0!==l&&l.lst[e.q.groupsetting.predefined_groupset_idx])for(const n of e.term.groupsetting.lst[e.q.groupsetting.predefined_groupset_idx]){if(!Array.isArray(n.values))throw"group.values[] not array from tw.term.groupsetting.lst[]";if(-1!=n.values.findIndex((e=>e.key==t)))return n.name}}(t[n.term.id],n);e&&(t[n.term.id]=e)}else if("integer"==n.term.type||"float"==n.term.type){const e=void t[n.term.id];e&&(t[n.term.id]=e)}}function q(t){for(const n of t)if(null==n.id||""==n.id){var e;if(null==n||null===(e=n.term)||void 0===e||!e.id)throw"tw.id and tw.term are both missing";n.id=n.term.id}else n.term||(n.term={id:n.id})}async function N(t,e,n,r){if(q(e),r){if(!Array.isArray(r))throw"geneTwLst not array";t.isoforms=[];for(const e of r){var s;if(null==e||null===(s=e.term)||void 0===s||!s.name)throw"gene tw missing .term.name";if(e.term.isoform)t.isoforms.push(e.term.isoform);else{var l,u;if("object"!=typeof t.genome)throw"serverside genome obj missing, needed to map gene name to canonical isoform";if(null===(l=t.genome)||void 0===l||null===(u=l.genedb)||void 0===u||!u.get_gene2canonicalisoform)throw"gene2canonicalisoform not supported on this genome";const n=t.genome.genedb.get_gene2canonicalisoform.get(e.term.name);if(null==n||!n.isoform)continue;t.isoforms.push(n.isoform)}}}"samples"==t.get&&((t.ssm_id_lst||t.isoform)&&(e.some((t=>"ssm.ssm_id"==t.id))||e.push({term:{id:"ssm.ssm_id"}}),e.some((t=>"case.observation.read_depth.t_alt_count"==t.id))||e.push({term:{id:"case.observation.read_depth.t_alt_count"}}),e.some((t=>"case.observation.read_depth.t_depth"==t.id))||e.push({term:{id:"case.observation.read_depth.t_depth"}}),e.some((t=>"case.observation.read_depth.n_depth"==t.id))||e.push({term:{id:"case.observation.read_depth.n_depth"}}),e.some((t=>"case.observation.sample.tumor_sample_uuid"==t.id))||e.push({term:{id:"case.observation.sample.tumor_sample_uuid"}})),r&&(e.some((t=>"case.submitter_id"==t.id))||e.push({term:{id:"case.submitter_id"}})),e.some((t=>"case.case_id"==t.id))||e.push({term:{id:"case.case_id"}})),"summary"!=t.get&&"sunburst"!=t.get||e.some((t=>"case.submitter_id"==t.id))||e.push({term:{id:"case.submitter_id"}});const f=[];for(const t of e){const e=n.cohort.termdb.q.termjsonByOneid(t.term.id);e&&f.push({term:e,q:t.q})}const d=e.map((t=>t.term.id));t.hiddenmclass&&(d.push("ssm.consequence.transcript.consequence_type"),d.push("ssm.consequence.transcript.transcript_id")),t.rglst&&(d.push("ssm.chromosome"),d.push("ssm.start_position"));const h={size:1e4,fields:d.join(",")};g(t,n),h.filters=L.filters(t,n);const p=x(t),m=await o.post(i.join(c,L.endpoint),{headers:p,body:JSON.stringify(h)});let y;delete t.isoforms;try{y=JSON.parse(m.body)}catch(t){throw"invalid JSON from GDC for variant2samples query"}if(!y.data||!y.data.hits)throw"variant2samples data structure not data.hits[]";if(!Array.isArray(y.data.hits))throw"variant2samples re.data.hits is not array for query";const b=[];for(const e of y.data.hits){if(!e.case)throw"variant2samples .case{} missing from a hit";const r={};if(e.ssm&&(r.ssm_id=e.ssm.ssm_id),t.hiddenmclass){var _;if(!Array.isArray(null===(_=e.ssm)||void 0===_?void 0:_.consequence))continue;const n={};if(v(n,e.ssm.consequence.find((e=>e.transcript.transcript_id==t.isoform))),t.hiddenmclass.has(n.class))continue}if(t.rglst){var w,N;if(null===(w=e.ssm)||void 0===w||!w.chromosome||null===(N=e.ssm)||void 0===N||!N.start_position)continue;if(!t.rglst.find((t=>t.chr==e.ssm.chromosome&&t.start<e.ssm.start_position&&t.stop>=e.ssm.start_position)))continue}var T,C,j,O;if(r.sample_id=await S(e.case,n,!0),e.case.case_id)r.sample_URLid=e.case.case_id,null!==(T=e.case)&&void 0!==T&&null!==(C=T.observation)&&void 0!==C&&null!==(j=C[0])&&void 0!==j&&null!==(O=j.sample)&&void 0!==O&&O.tumor_sample_uuid&&(r.sample_URLid=r.sample_URLid+"?bioId="+e.case.observation[0].sample.tumor_sample_uuid);for(const t of f)k(r,e.case,t);A(e.case,r),M(r,n),b.push(r)}if(r){const t={gene:r.map((t=>t.term.name)).join(","),twLst:f},e=await n.queries.geneCnv.bygene.get(t);for(const t of e)for(const e of t.samples)b.push(e)}const E=new Map;for(const t of b)a([t],E,t.ssm_id);return[...E.values()]}async function S(t,e,n){var r,o,i;return n&&t.submitter_id?t.submitter_id:null!=t&&null!==(r=t.observation)&&void 0!==r&&null!==(o=r[0])&&void 0!==o&&null!==(i=o.sample)&&void 0!==i&&i.tumor_sample_uuid?await e.aliquot2submitter.get(t.observation[0].sample.tumor_sample_uuid):t.case_id||t.submitter_id}function A(t,e){if(!t.observation)return;const n=t.observation[0];n&&n.read_depth&&(e.formatK2v={TumorAC:n.read_depth.t_depth-n.read_depth.t_alt_count+","+n.read_depth.t_alt_count,NormalDepth:n.read_depth.n_depth})}function M(t,e){var n;const r=t["case.project.project_id"];r&&(t.caseIsOpenAccess=null===(n=e.gdcOpenProjects)||void 0===n?void 0:n.has(r))}async function T(t,e,n,r){q(t);const i=[];for(const e of t)e.term&&"categorical"==e.term.type&&i.push({id:e.id,path:e.id.replace("case.","").replace(/\./g,"__"),type:e.term.type});const s=function(t){const e=[];for(const n of t)if(n.id)if(n.type="categorical")e.push(n.path+" {buckets { doc_count, key }}");else{if("integer"!=n.type&&"float"!=n.type)throw"unknown term type";e.push(n.path+" {stats { count }}")}return`query termislst2total( $filters: FiltersArgument) {\n\t\texplore {\n\t\t\tcases {\n\t\t\t\taggregations (filters: $filters, aggregations_filter_themselves: true) {\n\t\t\t\t\t${e.join("\n")}\n\t\t\t\t}\n\t\t\t}\n\t\t}\n\t}`}(i),a=function(t,e){const n={filters:{op:"and",content:[{op:"in",content:{field:"cases.available_variation_data",value:["ssm"]}}]}};if(t&&t.tid2value)for(const r in t.tid2value){e.cohort.termdb.q.termjsonByOneid(r)&&n.filters.content.push({op:"in",content:{field:r.replace(/^case\./,"cases."),value:[t.tid2value[r]]}})}t&&t.ssm_id_lst&&n.filters.content.push({op:"=",content:{field:"cases.gene.ssm.ssm_id",value:t.ssm_id_lst.split(",")}});return n}(e,r),l=await o.post(u,{headers:x(e),body:JSON.stringify({query:s,variables:a})});let c;try{c=JSON.parse(l.body)}catch(t){throw"invalid JSON from GDC for cohortTotal for query :"+s+" and filter: "+filter}const f=["data","explore","cases","aggregations"];let d=c[f[0]];for(let t=1;t<f.length;t++)if(d=d[f[t]],!d)throw"."+f[t]+" missing from data structure of termid2totalsize2 for query :"+s+" and filter: "+filter;for(const t of i){if("categorical"==t.type&&!Array.isArray(d[t.path].buckets))throw f.join(".")+" not array for query :"+s+" and filter: "+filter;if(("integer"==t.type||"float"==t.type)&&"object"!=typeof d[t.path].stats)throw f.join(".")+" not object for query :"+s+" and filter: "+filter}const h=new Map;for(const t of i)if("categorical"==t.type){const e=d[t.path].buckets;let n=[];for(const t of e)n.push([t.key.replace(".","__"),t.doc_count]);h.set(t.id,n)}else if("integer"==t.type||"float"==t.type){const e=d[t.path].stats.count;h.set(t.id,{total:e})}return n?[h,n]:h}function C(t){const e=["consequence.transcript.transcript_id","consequence.transcript.consequence_type","consequence.transcript.aa_change"];t.queries.snvindel.m2csq.get=async t=>{const n=await o(c+"/ssms/"+t.ssm_id+"?fields="+e.join(","),{method:"GET",headers:x(t)});let r;try{r=JSON.parse(n.body)}catch(t){throw"invalid json in response"}if(!r.data||!r.data.consequence)throw"returned data not .data.consequence";if(!Array.isArray(r.data.consequence))throw".data.consequence not array";return r.data.consequence.map((t=>t.transcript))}}function j(t,e){t.queries.singleSampleMutation.get=async(n,r)=>{if(!n)throw"sampleName missing";return r.case_id=await async function(t){const e=await o.post("https://api.gdc.cancer.gov/cases",{headers:{"Content-Type":"application/json",Accept:"application/json"},body:JSON.stringify({size:1,fields:"case_id,submitter_id",filters:{op:"or",content:[{op:"=",content:{field:"samples.portions.analytes.aliquots.aliquot_id",value:[t]}},{op:"=",content:{field:"submitter_id",value:[t]}},{op:"=",content:{field:"samples.submitter_id",value:[t]}}]}})}),n=JSON.parse(e.body);for(const t of n.data.hits)if(t.case_id)return t.case_id;throw"cannot convert to case_id (uuid)"}(n),await E(r,t,e)}}function O(t){return async(e,n)=>{try{const r=t[e.query.genome];if(!r)throw"invalid genome";const o=r.datasets[e.query.dslabel];if(!o)throw"invalid dslabel";if(!e.query.case_id)throw".case_id missing";n.send({mlst:await E(e.query,o,r)})}catch(t){t.stack&&console.log(t.stack),n.send({error:t.message||t})}}}async function E(t,e,n){const s=[];{const e=await o.post(i.join(c,F.endpoint),{headers:x(t),body:JSON.stringify({size:1e3,fields:F.fields.join(","),filters:F.filters(t)})}),a=JSON.parse(e.body);for(const t of a.data.hits){let e;for(const n of t.consequence)if(n.transcript&&n.transcript.gene&&n.transcript.gene.symbol){e=n.transcript.gene.symbol;break}if(!e)continue;const o=n.genedb.get_gene2canonicalisoform.get(e);if(null==o||!o.isoform)continue;let i=t.consequence.find((t=>t.transcript.transcript_id==o.isoform));i||(i=t.consequence[0]);const a=i.transcript.aa_change||i.transcript.consequence_type,[l,c,u]=r.vepinfo(i.transcript.consequence_type);s.push({dt:r.dtsnvindel,mname:a,class:c,gene:i.transcript.gene.symbol,chr:t.chromosome,pos:t.start_position,ref:t.reference_allele,alt:t.tumor_allele})}}{const e=await async function(t){const e=x(t),n=await o.post(i.join(c,"files"),{headers:e,body:JSON.stringify({size:1e4,fields:["cases.samples.sample_type","data_type","file_id","data_format","experimental_strategy","analysis.workflow_type"].join(","),filters:function(t){if(!t.case_id)throw".case_id missing";return{op:"and",content:[{op:"in",content:{field:"cases.case_id",value:[t.case_id]}},{op:"in",content:{field:"data_type",value:["Masked Copy Number Segment","Copy Number Segment","Transcript Fusion"]}}]}}(t)})}),s=JSON.parse(n.body);if(!Array.isArray(s.data.hits))throw"re.data.hits[] not array";let a,l,u;for(const t of s.data.hits)if("BEDPE"!=t.data_format){if("TXT"==t.data_format){if("Genotyping Array"==t.experimental_strategy){var f,d,h;const e=null===(f=t.cases)||void 0===f||null===(d=f[0].samples)||void 0===d||null===(h=d[0])||void 0===h?void 0:h.sample_type;if(!e)continue;if(e.includes("Normal"))continue;if("Masked Copy Number Segment"!=t.data_type)continue;a=t.file_id;continue}if("WGS"==t.experimental_strategy){if(!t.file_id)continue;if("Copy Number Segment"!=t.data_type)continue;l=t.file_id;continue}}}else{var p;if("RNA-Seq"!=t.experimental_strategy)continue;if("Arriba"!=(null===(p=t.analysis)||void 0===p?void 0:p.workflow_type))continue;if("Transcript Fusion"!=t.data_type)continue;u=t.file_id}const m=[];if(l){const t=(await o(i.join(c,"data")+"/"+l,{method:"GET",headers:e})).body.split("\n");for(let e=1;e<t.length;e++){const n=t[e].split("\t");if(7!=n.length)continue;const o=Number(n[4]),i=Number(n[5]),s=Number(n[6]);if(Number.isNaN(o)||Number.isNaN(i)||Number.isNaN(s))continue;const a={dt:r.dtcnv,chr:n[1],start:Number(n[2]),stop:Number(n[3]),value:o};!a.chr||Number.isNaN(a.start)||Number.isNaN(a.stop)||(m.push(a),o>0&&0==s&&i>0&&m.push({dt:r.dtloh,chr:a.chr,start:a.start,stop:a.stop,segmean:.5}))}}else if(a){const t=(await o(i.join(c,"data")+"/"+a,{method:"GET",headers:e})).body.split("\n");for(let e=1;e<t.length;e++){const n=t[e].split("\t");if(6!=n.length)continue;if(!n[1])continue;const o={dt:r.dtcnv,chr:"chr"+n[1],start:Number(n[2]),stop:Number(n[3]),value:Number(n[5])};Number.isNaN(o.start)||Number.isNaN(o.stop)||Number.isNaN(o.value)||m.push(o)}}if(u)try{const t=(await o(i.join(c,"data")+"/"+u,{method:"GET",headers:e})).body.split("\n");for(let e=1;e<t.length;e++){const n=t[e].split("\t"),o={dt:r.dtfusionrna,chrA:n[0],posA:Number(n[1]),chrB:n[3],posB:Number(n[4])};o.chrA&&o.chrB&&!Number.isNaN(o.posA)&&!Number.isNaN(o.posB)&&(w(o,n[6]),m.push(o))}}catch(t){}return m}(t);s.push(...e)}return s}function R(t){return async(e,n)=>{try{if(!t[e.query.genome])throw"invalid genome";n.send({genes:await I({filter:e.query.filter0,CGConly:parseInt(e.query.CGConly),maxGenes:e.query.maxGenes})})}catch(t){t.stack&&console.log(t.stack),n.send({error:t.message||t})}}}async function I({filter:t,CGConly:e,maxGenes:n}){let r={op:"and",content:[]};if(t){if("object"!=typeof t)throw"filter not object";r=t}const s=await o.post(i.join(c,"/analysis/top_mutated_genes_by_project"),{headers:{"Content-Type":"application/json",Accept:"application/json"},body:JSON.stringify({size:n||50,fields:"symbol",filters:P(r,e)})}),a=JSON.parse(s.body),l=[];for(const t of a.data.hits)t.symbol&&l.push(t.symbol);return l}function P(t,e){let n;if("in"==t.op)n={op:"and",content:[t]};else{if("and"!=t.op)throw'f.op not "in" or "and"';n=t}return n.content.push({op:"NOT",content:{field:"ssms.consequence.transcript.annotation.vep_impact",value:"missing"}}),n.content.push({op:"in",content:{field:"ssms.consequence.transcript.consequence_type",value:["missense_variant","frameshift_variant","start_lost","stop_lost","stop_gained"]}}),e&&n.content.push({op:"in",content:{field:"genes.is_cancer_gene_census",value:["true"]}}),n}const F={endpoint:"/ssms",size:1e5,fields:["ssm_id","chromosome","start_position","reference_allele","tumor_allele","consequence.transcript.transcript_id","consequence.transcript.consequence_type","consequence.transcript.aa_change","consequence.transcript.gene.symbol"],filters:t=>{const e={op:"and",content:[]};if(t.isoform){if("string"!=typeof t.isoform)throw".isoform value not string";e.content.push({op:"=",content:{field:"consequence.transcript.transcript_id",value:[t.isoform]}})}if(t.case_id){if("string"!=typeof t.case_id)throw".case_id value not string";e.content.push({op:"=",content:{field:"cases.case_id",value:[t.case_id]}})}if(t.set_id){if("string"!=typeof t.set_id)throw".set_id value not string";e.content.push({op:"in",content:{field:"cases.case_id",value:[t.set_id]}})}return t.filter0&&e.content.push(t.filter0),t.filterObj&&e.content.push(l(t.filterObj)),e}},L={endpoint:"/ssm_occurrences",size:1e5,fields:["ssm.ssm_id","case.case_id","case.submitter_id","case.observation.sample.tumor_sample_uuid"],filters:(t,e)=>{const n={op:"and",content:[]};if(t.ssm_id_lst){if("string"!=typeof t.ssm_id_lst)throw"ssm_id_lst not string";n.content.push({op:"=",content:{field:"ssm.ssm_id",value:t.ssm_id_lst.split(",")}})}else if(t.isoform)n.content.push({op:"=",content:{field:"ssms.consequence.transcript.transcript_id",value:[t.isoform]}});else{if(!t.isoforms)throw".ssm_id_lst, .isoform, .isoforms are all missing";if(!Array.isArray(t.isoforms))throw".isoforms[] not array";n.content.push({op:"in",content:{field:"ssms.consequence.transcript.transcript_id",value:t.isoforms}})}if(t.rglst&&(n.content.push({op:">=",content:{field:"ssms.start_position",value:t.rglst[0].start}}),n.content.push({op:"<=",content:{field:"ssms.start_position",value:t.rglst[0].stop}})),t.set_id){if("string"!=typeof t.set_id)throw".set_id value not string";n.content.push({op:"in",content:{field:"cases.case_id",value:[t.set_id]}})}if(t.filter0&&n.content.push(t.filter0),t.filterObj&&n.content.push(l(t.filterObj)),t.tid2value)for(const r in t.tid2value){const o=e.cohort.termdb.q.termjsonByOneid(r);if(o)if("categorical"==o.type)n.content.push({op:"in",content:{field:r,value:[t.tid2value[r]]}});else if("integer"==o.type)for(const e of t.tid2value[r])n.content.push({op:e.op,content:{field:r,value:e.range}})}return n}}},9535:(t,e,n)=>{"use 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cnv.byrange";n.byrange.file=s.join(h.tpmasterdir,n.byrange.file),n.byrange.get=await W(t,e),P(t,n.byrange.samples,"cnv.byrange")}}(t,e),await async function(t,e){const n=t.queries.ld;if(!n)return;if(!Array.isArray(n.tracks)||!n.tracks.length)throw"ld.tracks[] not nonempty array";for(const t of n.tracks){if(!t.name)throw"name missing from one of ld.tracks[]";if(!t.file)throw".file missing from one of ld.tracks[]";t.file0=t.file,t.file=s.join(h.tpmasterdir,t.file),await f.validate_tabixfile(t.file),t.nochr=await f.tabix_is_nochr(t.file,null,e)}if(!n.overlay)throw"ld.overlay{} missing";if(!n.overlay.color_0)throw"ld.overlay.color_0 missing";if(!n.overlay.color_1)throw"ld.overlay.color_1 missing"}(t,e),await async function(t,e){const n=t.queries.geneExpression;if(!n)return;if(n.gdcapi)return void r.validate_query_geneExpression(t);if(!n.file)throw".file missing from queries.geneExpression";n.file=s.join(h.tpmasterdir,n.file),await f.validate_tabixfile(n.file),n.nochr=await f.tabix_is_nochr(n.file,null,e),n.get=async e=>{let r;{const n=await z(e,null,t);n&&(r=new Set(n.map((t=>t.name))))}const o=new Map;for(const t of e.genes)o.set(t.gene,{}),await f.get_lines_bigfile({args:[n.file,(n.nochr?t.chr.replace("chr",""):t.chr)+":"+t.start+"-"+t.stop],dir:n.dir,callback:e=>{const n=e.split("\t");let i;try{i=JSON.parse(n[3])}catch(t){return}i.gene==t.gene&&(r&&!r.has(i.sample)||(o.get(t.gene)[i.sample]=i.value))}});return o}}(t,e),await async function(t,e){const n=t.queries.singleSampleMutation;if(!n)return;if(n.gdcapi)r.validate_query_singleSampleMutation(t,e);else{if(!n.folder)throw"unknown query method for singleSampleMutation";n.get=async e=>{var r,o,i;let a=e;if(null!==(r=t.cohort)&&void 0!==r&&null!==(o=r.termdb)&&void 0!==o&&null!==(i=o.q)&&void 0!==i&&i.sampleName2id&&(a=t.cohort.termdb.q.sampleName2id(e),null==a))return[];const l=await f.read_file(s.join(h.tpmasterdir,n.folder,a.toString()));return JSON.parse(l)}}}(t,e),await async function(t,e){const n=t.queries.singleSampleGenomeQuantification;if(!n)return;for(const r in n){if(!Number.isFinite(n[r].min))throw"min not a number";if(!Number.isFinite(n[r].max))throw"max not a number";if(n[r].min>=n[r].max)throw"min>=max";if(!n[r].folder)throw"unknown query method for singleSampleGenomeQuantification";n[r].get=async(o,i)=>{var a,l,c;let u=o;if(null!==(a=t.cohort)&&void 0!==a&&null!==(l=a.termdb)&&void 0!==l&&null!==(c=l.q)&&void 0!==c&&c.sampleName2id&&(u=t.cohort.termdb.q.sampleName2id(o),null==u))return[];return await U(s.join(h.tpmasterdir,n[r].folder,u.toString()),e,n[r],i)}}}(t,e),await async function(t,e){const n=t.queries.singleSampleGbtk;if(!n)return;for(const e in n){if(!Number.isFinite(n[e].min))throw"min not a number";if(!Number.isFinite(n[e].max))throw"max not a number";if(n[e].min>=n[e].max)throw"min>=max";if(!n[e].folder)throw"unknown query method for singleSampleGbtk";n[e].get=async r=>{var i,a,l;let c=r;if(null!==(i=t.cohort)&&void 0!==i&&null!==(a=i.termdb)&&void 0!==a&&null!==(l=a.q)&&void 0!==l&&l.sampleName2id&&(c=t.cohort.termdb.q.sampleName2id(r),null==c))return{};const u=s.join(n[e].folder,c+".gz");try{return await o.promises.stat(s.join(h.tpmasterdir,u)),{path:u}}catch(t){return{}}}}}(t),u(t),function(t){if(!t.ssm2canonicalisoform)return;if(t.ssm2canonicalisoform.gdcapi)return void r.validate_ssm2canonicalisoform(t.ssm2canonicalisoform);throw"ssm2canonicalisoform.gdcapi is false"}(t),function(t,e){if(!e.genedb.hasTable_refseq2ensembl)return;t.refseq2ensembl_query=e.genedb.db.prepare("select ensembl from refseq2ensembl where refseq=?")}(t,e),function(t,e){if(!t.queries.snvindel&&!t.queries.svfusion&&!t.queries.geneCnv)return;t.mayGetGeneVariantData=async(n,r)=>{if("object"!=typeof n.term)throw"tw.term{} is not object";if("geneVariant"!=n.term.type)throw"tw.term.type is not geneVariant";if("string"!=typeof n.term.name)throw"tw.term.name is not string";if(!n.term.name)throw"tw.term.name should be gene symbol but is empty string";const o=[];if(t.queries.snvindel){const i=await async function(t,e,n,r){const o={addFormatValues:!0,filter0:r.filter0,filterObj:r.filter};t.queries.geneCnv&&(o.useCaseid4sample=!0);if(t.queries.snvindel.byisoform)return await async function(t,e){if(t.isoform&&"string"==typeof t.isoform)return;if(!t.name)throw"both term.name and term.isoform";const n=e.genedb.getjsonbyname.all(t.name);if(0==n.length)return;const r=n.find((t=>t.isdefault))||n[0],o=JSON.parse(r.genemodel);if(!o.isoform)throw"isoform missing from returned gm";t.isoform=o.isoform}(e,n),e.isoform?(o.isoform=e.isoform,await t.queries.snvindel.byisoform.get(o)):[];if(t.queries.snvindel.byrange)return await V(e,n),o.rglst=[e],await t.queries.snvindel.byrange.get(o);throw"unknown queries.snvindel method"}(t,n.term,e,r);o.push(...i)}if(t.queries.svfusion){const i=await async function(t,e,n,r){const o={addFormatValues:!0,filter0:r.filter0,filterObj:r.filter};if(t.queries.svfusion.byrange)return await V(e,n),o.rglst=[e],await t.queries.svfusion.byrange.get(o);throw"unknown queries.svfusion method"}(t,n.term,e,r);o.push(...i)}if(t.queries.cnv){const i=await async function(t,e,n,r){var o,i,s;const a={addFormatValues:!0,filter0:r.filter0,filterObj:r.filter,cnvMaxLength:null==e||null===(o=e.q)||void 0===o?void 0:o.cnvMaxLength,cnvGainCutoff:null==e||null===(i=e.q)||void 0===i?void 0:i.cnvGainCutoff,cnvLossCutoff:null==e||null===(s=e.q)||void 0===s?void 0:s.cnvLossCutoff};if(t.queries.cnv.byrange)return await V(e.term,n),a.rglst=[e.term],await t.queries.cnv.byrange.get(a);throw"unknown queries.cnv method"}(t,n,e,r);o.push(...i)}if(t.queries.geneCnv){const e=await async function(t,e,n,r){const o={filter0:r.filter0};if(t.queries.geneCnv.bygene)return e.name?(o.gene=e.name,await t.queries.geneCnv.bygene.get(o)):[];throw"unknown queries.geneCnv method"}(t,n.term,0,r);o.push(...e)}const i=new Map;for(const e of o)if(Array.isArray(e.samples))for(const r of e.samples){var s,a;if(i.has(r.sample_id)||i.set(r.sample_id,{sample:r.sample_id}),null!==(s=t.cohort)&&void 0!==s&&null!==(a=s.termdb)&&void 0!==a&&a.additionalSampleAttributes)for(const e of t.cohort.termdb.additionalSampleAttributes)e in r&&(i.get(r.sample_id)[e]=r[e]);i.get(r.sample_id)[n.term.name]||(i.get(r.sample_id)[n.term.name]={key:n.term.name,label:n.term.name,values:[]});const o={gene:n.term.name,isoform:e.isoform,dt:e.dt,chr:n.term.chr,class:e.class,pos:e.pos||(e.start?e.start+"-"+e.stop:""),mname:e.mname,_SAMPLEID_:r.sample_id,_SAMPLENAME_:r.sample_id};if("value"in e&&(o.value=e.value),r.formatK2v)for(const t in r.formatK2v)o[t]=r.formatK2v[t];e.dt==p||e.dt==m||e.dt,t.cohort.termdb.q.id2sampleName&&Number.isInteger(r.sample_id)&&(o._SAMPLENAME_=t.cohort.termdb.q.id2sampleName(r.sample_id)),i.get(r.sample_id)[n.term.name].values.push(o)}return await async function(t,e,n,r){var o;if(null===(o=e.assayAvailability)||void 0===o||!o.byDt)return;const i=t.filter?new Set((await x(t.filter,e)).map((t=>t.id))):null;for(const t in e.assayAvailability.byDt){const o=e.assayAvailability.byDt[t];if(o.byOrigin)for(const e in o.byOrigin){J(t,o.byOrigin[e],n,r,e,i)}else J(t,o,n,r,!1,i)}}(r,t,i,n.term.name),i}}(t,e)),function(t){if(!t.assayAvailability)return;if(t.assayAvailability.byDt)for(const e in t.assayAvailability.byDt){const n=t.assayAvailability.byDt[e];if(n.byOrigin)for(const e in n.byOrigin){const r=n.byOrigin[e];if(!r.yes||!r.no||!r.term_id)throw"ds.assayAvailability.byDt.*.byOrigin properties require .term_id .yes{} .no{}";Y(t,r)}else{if(!n.yes||!n.no||!n.term_id)throw"ds.assayAvailability.byDt properties require .term_id .yes{} .no{}";Y(t,n)}}}(t),null!==(l=t.cohort)&&void 0!==l&&null!==(c=l.db)&&void 0!==c&&c.refresh&&i&&N(t,i,a)}function E(t){var e;const n={isMds3:!0,label:t.label};if(function(t,e){if(!t.queries)return;const n={};t.queries.singleSampleMutation&&(n.singleSampleMutation={sample_id_key:t.queries.singleSampleMutation.sample_id_key,discoSkipChrM:t.queries.singleSampleMutation.discoSkipChrM});if(t.queries.singleSampleGenomeQuantification){n.singleSampleGenomeQuantification={};for(const e in t.queries.singleSampleGenomeQuantification)n.singleSampleGenomeQuantification[e]=JSON.parse(JSON.stringify(t.queries.singleSampleGenomeQuantification[e])),delete n.singleSampleGenomeQuantification[e].folder}if(t.queries.singleSampleGbtk){n.singleSampleGbtk={};for(const e in t.queries.singleSampleGbtk)n.singleSampleGbtk[e]=JSON.parse(JSON.stringify(t.queries.singleSampleGbtk[e])),delete n.singleSampleGbtk[e].folder}const r=t.queries.snvindel;r&&(e.has_skewer=!0,n.snvindel={forTrack:r.forTrack,vcfid4skewerName:r.vcfid4skewerName,variantUrl:r.variantUrl,skewerRim:r.skewerRim},r.m2csq&&(n.snvindel.m2csq={by:r.m2csq.by}),r.info&&(e.bcf={info:r.info}),r.format&&(e.bcf||(e.bcf={}),e.bcf.format=r.format));if(t.queries.ld){n.ld=JSON.parse(JSON.stringify(t.queries.ld));for(const t of n.ld.tracks)delete t.file}e.queries=n}(t,n),null!==(e=t.cohort)&&void 0!==e&&e.termdb&&(n.termdb={},t.cohort.termdb.allowCaseDetails&&(n.termdb.allowCaseDetails={sample_id_key:t.cohort.termdb.allowCaseDetails.sample_id_key})),t.variant2samples){const e=t.variant2samples;n.variant2samples={sunburst_twLst:e.sunburst_twLst,twLst:e.twLst,type_samples:e.type_samples,type_summary:e.type_summary,type_sunburst:e.type_sunburst,url:e.url,variantkey:e.variantkey}}return n}async function R(t){var e,o,i,s;if(t.cohort){if(!t.cohort.termdb)throw"ds.cohort is set but cohort.termdb{} missing";if(!t.cohort.db)throw"ds.cohort is set but cohort.db{} missing";if(!t.cohort.db.file&&!t.cohort.db.file_fullpath)throw"ds.cohort.db.file missing"}else{if(!t.termdb)return;t.cohort={},t.cohort.termdb=t.termdb,delete t.termdb}const a=t.cohort.termdb;if(null!=a&&null!==(e=a.dictionary)&&void 0!==e&&e.gdcapi)await c(t);else if(null!=a&&null!==(o=a.dictionary)&&void 0!==o&&o.dbFile)t.cohort.db={file:a.dictionary.dbFile},delete a.dictionary.dbFile,k(t);else{if(!t.cohort.db)throw"unknown method to initiate dictionary";k(t)}if(a.termid2totalsize2&&(a.termid2totalsize2.gdcapi,a.termid2totalsize2.get=async(e,n={},o=null)=>a.termid2totalsize2.gdcapi?await r.get_termlst2size(e,n,o,t):await async function(t,e,n,r){const o=new Map;for(const n of t)if(n.term&&"categorical"==n.term.type){var i,s;const t={term1_id:n.id,term1_q:{type:"values"}};e.tid2value&&(t.filter=Z(e.tid2value,r));const a=await q(t,r,r.cohort.termdb);if(null==a||null===(i=a.data)||void 0===i||null===(s=i.charts)||void 0===s||!s[0])continue;const l=[];for(const t of a.data.charts[0].serieses)l.push([t.seriesId,t.total]);o.set(n.id,l)}return n?[o,n]:o}(e,n,o,t)),function(t){const e=t.selectCohort;if(!e)return;if("object"!=typeof e)throw"selectCohort{} not object";if(!e.term)throw"term{} missing from termdb.selectCohort";if(!e.term.id)throw"id missing from termdb.selectCohort.term";if("string"!=typeof e.term.id)throw"termdb.selectCohort.term.id is not string";if("categorical"!=e.term.type)throw'type is not hardcoded "categorical" from termdb.selectCohort.term';{const n=t.q.termjsonByOneid(e.term.id);if(!n)throw"termdb.selectCohort.term.id is invalid";if("categorical"!=n.type)throw"termdb.selectCohort.term type is not categorical"}if(!e.values)throw"values[] missing from termdb.selectCohort";if(!Array.isArray(e.values))throw"termdb.selectCohort.values is not array";if(0==e.values.length)throw"termdb.selectCohort.values[] cannot be empty";for(const t of e.values){if(!t.keys)throw"keys[] missing from one of selectCohort.values[]";if(!Array.isArray(t.keys))throw"keys[] is not array from one of selectCohort.values[]";if(0==t.keys.length)throw"keys[] is empty from one of selectCohort.values[]"}}(a),await async function(t){if(!t.restrictAncestries)return;if(!Array.isArray(t.restrictAncestries)||0==t.restrictAncestries.length)throw"termdb.restrictAncestries[] is not non-empty array";for(const e of t.restrictAncestries){if(!e.name)throw"name missing from one of restrictAncestries";if("object"!=typeof e.tvs)throw".tvs{} missing from one of restrictAncestries";if(!e.tvs.term)throw"tvs.term{} missing from an ancestry";if(!e.tvs.term.id)throw"tvs.term.id missing from an ancestry";{const n=t.q.termjsonByOneid(e.tvs.term.id);if(!n)throw"tvs.term.id is invalid from an ancestry";if("categorical"!=n.type)throw"tvs.term.type is not categorical from an ancestry"}if(!Number.isInteger(e.PCcount))throw"PCcount is not integer";if(e.PCfile)e.pcs=await I(e.PCfile,e.PCcount);else if(e.PCfileBySubcohort){if(!t.selectCohort)throw"PCfileBySubcohort is in use but selectCohort is not enabled";for(const n in e.PCfileBySubcohort){let r=!0;for(const e of t.selectCohort.values)if(n==e.keys.sort().join(",")){r=!1;break}if(r)throw"unknown subcohort from PCfileBySubcohort";const o=e.PCfileBySubcohort[n];if(!o.file)throw".file missing for a subcohort in PCfileBySubcohort";o.pcs=await I(o.file,e.PCcount)}}}}(a),await S(t),await A(t),"minTimeSinceDx"in a){if(!Number.isFinite(a.minTimeSinceDx))throw"termdb.minTimeSinceDx not number";if(a.minTimeSinceDx<=0)throw"termdb.minTimeSinceDx<=0"}if("ageEndOffset"in a){if(!Number.isFinite(a.ageEndOffset))throw"termdb.ageEndOffset not number";if(a.ageEndOffset<=0)throw"termdb.ageEndOffset<=0"}if(t.cohort.termdb.additionalSampleAttributes){if(!Array.isArray(t.cohort.termdb.additionalSampleAttributes))throw"termdb.additionalSampleAttributes not array";for(const e of t.cohort.termdb.additionalSampleAttributes)if("string"!=typeof e)throw"non-str key in termdb.additionalSampleAttributes[]"}if(null!==(i=t.cohort)&&void 0!==i&&null!==(s=i.db)&&void 0!==s&&s.connection){t.sampleName2Id=new Map,t.sampleId2Name=new Map;const e="SELECT * FROM sampleidmap",n=t.cohort.db.connection.prepare(e).all();for(const e of n)t.sampleId2Name.set(e.id,e.name),t.sampleName2Id.set(e.name,e.id);t.getSampleIdMap=e=>{const n={};for(const r in e)n[r]=t.sampleId2Name.get(+r);return n}}if(t.cohort.mutationset){const{mayGetGeneVariantData:e,getTermTypes:r,mayGetMatchingGeneNames:o}=n(7833);t.mayGetGeneVariantData=e,t.getTermTypes=r,t.mayGetMatchingGeneNames=o}}async function I(t,e){const n=new Map;for(let t=1;t<=e;t++)n.set(C+t,new Map);let r=0;for(const o of(await f.read_file(s.join(h.tpmasterdir,t))).trim().split("\n")){r++;const t=o.split("\t"),i=Number(t[0]);if(!Number.isInteger(i))throw"non-integer sample id from a line of restrictAncestries pc file";for(let r=1;r<=e;r++){const e=C+r,o=Number(t[r]);if(Number.isNaN(o))throw"non-numeric PC value from restrictAncestries file";n.get(e).set(i,o)}}return console.log(r,"samples loaded from "+t),Object.freeze(n)}function P(t,e,n){var r;if(!e)return;let o;if(null!=t&&null!==(r=t.cohort)&&void 0!==r&&r.termdb){for(const t of e){const e=Number(t.name);if(!Number.isInteger(e))throw"non-integer sample id from "+n;t.name=e}o=", all integer IDs"}console.log(e.length,"samples from "+n+" of "+t.label+o)}async function F(t,e){var n;const r=t.queries.snvindel.byrange;if(r._tk.file)await f.init_one_vcf(r._tk,e,!0);else if(r._tk.chr2files){let t;for(const n in r._tk.chr2files){if("chr17"!=n)continue;const o=r._tk.chr2files[n];try{await f.init_one_vcf(o,e,!0);const i=JSON.stringify(o.samples);if(t){if(i!=t)throw"Different samples found in bcf file of "+n}else t=i,r._tk.samples=o.samples,r._tk.format=o.format,r._tk.info=o.info,r._tk.nochr=o.nochr}catch(t){console.log("missing file ignored:",o.file)}}}if(null!==(n=r._tk)&&void 0!==n&&n.samples.length){if(!r._tk.format)throw"bcf file has 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t.queries.snvindel.info=r._tk.info,t.queries.snvindel.format=r._tk.format,async e=>{if(!Array.isArray(e.rglst))throw"q.rglst[] is not array";if(0==e.rglst.length)throw"q.rglst[] blank array";const n=L(e);let o;if(r._tk.chr2files){const t=r._tk.chr2files[e.rglst[0].chr];if(!t)throw"unknown chr for chr2files";o=t.file}else o=r._tk.file||r._tk.url;const i=["query",o,"-r",e.rglst.map((t=>(r._tk.nochr?t.chr.replace("chr",""):t.chr)+":"+t.start+"-"+(t.stop+1))).join(","),"-f","%ID\t%CHROM\t%POS\t%REF\t%ALT\t%INFO\t%FORMAT\n"],s=await z(e,r._tk.samples,t);s&&i.push("-s",s.map((t=>t.name)).join(",")),e.variantFilter&&M(e.variantFilter,i);const a=[];return await f.get_lines_bigfile({isbcf:!0,args:i,dir:r._tk.dir,callback:o=>{const i=o.split("\t"),l=i[0],c=i[1],u=Number(i[2]),f=i[3],h=i[4].split(","),p=i[5],m={pos:u-1};d(r._tk,f,h,m,p,l,e.isoform);for(const o of m.mlst){var g,y,v;e.hiddenmclass&&e.hiddenmclass.has(o.class)||(D(o,e)||m.mlst.length>1&&null!==(g=e.variantFilter)&&void 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n=t._tk.format[e];if(!n)throw"invalid format field: "+n;a.push(n)}const l=[];for(const[e,o]of(i||t._tk.samples).entries()){const t=n[e+7];if(!t||"."==t)continue;const i=G(t.split(":"),a,o,r);if(i){if(s){let t=!1;for(const e in s){const n=e in i.formatK2v?i.formatK2v[e]:j;if(s[e].has(n)){t=!0;break}}if(t)continue}l.push(i)}}l.length&&(e.samples=l)}function G(t,e,n,r){const o={};for(const[n,r]of e.entries()){const e=t[n];if(e&&"."!=e)if(r.isGT){if("./."==e||".|."==e)continue;o.GT=e}else o[r.ID]=e}if(0==Object.keys(o).length)return null;const i={sample_id:n.name};return r&&(i.formatK2v=o),i}function U(t,e,n,r=1){r=Number(r);const s=200,c=20;let u=0;for(const t in e.majorchr)u+=e.majorchr[t];const f=800/u,d={};let h=0;const p=[];for(const t in e.majorchr){const n=e.majorchr[t];d[t]=a().domain([0,n]).range([f*h,f*(h+n)]),h+=n,p.push({chr:t,chrLen:n,xStart:f*(h-n),xStop:f*h})}const m=a().domain([n.min,n.max]).range([s,0]),g=l(890*r,240*r),y=g.getContext("2d");r>1&&y.scale(r,r),b(n.max),b(0),b(n.min);const v=i.createInterface({input:o.createReadStream(t)});return new Promise(((t,r)=>{v.on("line",(t=>{const e=t.split("\t"),r=e[0];if(!r)return;if(!d[r])return;const o=Number(e[1]);if(!Number.isInteger(o))return;const i=Number(e[2]);if(!Number.isFinite(i))return;if(i<n.min||i>n.max)return;y.fillStyle=i>0?n.positiveColor:n.negativeColor;const s=d[r](o),a=c+m(i);y.fillRect(70+s,a,1,1)})),v.on("close",(()=>{!function(){y.strokeStyle="black",y.beginPath();{const t=220-m(0);y.moveTo(70,t),y.lineTo(870,t),y.stroke()}let t=!0;y.fillStyle="black",y.font="12px Arial",y.textAlign="center";for(const n in d){if(y.fillText(n.replace("chr",""),70+d[n](e.majorchr[n]/2),234),t){t=!1;continue}const r=Math.floor(70+d[n](0))+.5;y.moveTo(r,c),y.lineTo(r,220),y.stroke()}y.closePath()}(),t({src:g.toDataURL(),canvasWidth:890,canvasHeight:240,xoff:70,chrLst:p})}))}));function b(t){y.fillStyle="black",y.font="12px Arial",y.textAlign="right";const e=c+m(t);y.fillText(t,64,e+5),y.strokeStyle="black",y.beginPath(),y.moveTo(66,e),y.lineTo(70,e),y.stroke(),y.closePath()}}async function H(t,e){const n=t.queries.svfusion.byrange;if(n.file)await f.validate_tabixfile(n.file);else{if(!n.url)throw"file and url both missing on svfusion.byrange{}";n.dir=await f.cache_index(n.url,n.indexURL)}n.nochr=await f.tabix_is_nochr(n.file||n.url,null,e);{const t=await f.get_header_tabix(n.file);if(!t[0])throw"header line missing from "+n.file;const e=t[0].split(" ");if("#sample"!=e[0])throw"header line not starting with #sample: "+n.file;n.samples=e.slice(1).map((t=>({name:t})))}return async e=>{if(!Array.isArray(e.rglst))throw"q.rglst[] is not array";if(0==e.rglst.length)throw"q.rglst[] blank array";const r=L(e);let o;{const r=await z(e,n.samples,t);r&&(o=new Set(r.map((t=>t.name))))}const i=new Map;for(const t of e.rglst)await f.get_lines_bigfile({args:[n.file||n.url,(n.nochr?t.chr.replace("chr",""):t.chr)+":"+t.start+"-"+t.stop],dir:n.dir,callback:n=>{const s=n.split("\t"),a=Number(s[1]);let l,c,u,f,d;try{l=JSON.parse(s[3])}catch(t){return}if(l.dt!=m&&l.dt!=g)return;if(l.class=l.dt==g?b:v,e.hiddenmclass&&e.hiddenmclass.has(l.class))return;if(l.sample&&o&&!o.has(l.sample))return;if(l.chrA)c=1,u=l.geneA||l.chrA,f=l.strandA,d=[{a:{chr:l.chrA,pos:l.posA,strand:l.strandA,name:l.geneA},b:{chr:t.chr,pos:a,strand:l.strandB,name:l.geneB}}];else if(l.chrB)c=0,u=l.geneB||l.chrB,f=l.strandB,d=[{a:{chr:t.chr,pos:a,strand:l.strandA,name:l.geneA},b:{chr:l.chrB,pos:l.posB,strand:l.strandB,name:l.geneB}}];else{if(!l.pairlst)throw"missing chrA and chrB";{d=l.pairlst;const t=l.pairlst.findIndex((t=>t.chr==chr&&t.pos==a));if(-1==t)throw"current point missing from pairlst";c=t}}const h=[l.dt,t.chr,a,f,c,encodeURIComponent(u)].join(T);let p;if(l.sample&&(p={sample_id:l.sample},l.mattr)){if(r)for(const t in r){const e=t in l.mattr?l.mattr[t]:j;if(r[t].has(e))return}e.addFormatValues&&(p.formatK2v=l.mattr)}i.has(h)||i.set(h,{ssm_id:h,dt:l.dt,class:l.class,chr:t.chr,pos:a,strand:f,pairlstIdx:c,mname:u,pairlst:d,samples:[]}),p&&i.get(h).samples.push(p)}});return[...i.values()]}}async function W(t,e){const n=t.queries.cnv.byrange;if(n.file)await f.validate_tabixfile(n.file);else{if(!n.url)throw"file and url both missing on cnv.byrange{}";n.dir=await f.cache_index(n.url,n.indexURL)}n.nochr=await f.tabix_is_nochr(n.file||n.url,null,e);{const t=await f.get_header_tabix(n.file);if(!t[0])throw"header line missing from "+n.file;const e=t[0].split(" ");if("#sample"!=e[0])throw"header line not starting with #sample: "+n.file;n.samples=e.slice(1).map((t=>({name:t})))}return async e=>{if(!Array.isArray(e.rglst))throw"q.rglst[] is not array";if(0==e.rglst.length)throw"q.rglst[] blank array";if(e.cnvMaxLength&&!Number.isInteger(e.cnvMaxLength))throw"cnvMaxLength is not integer";if(e.cnvGainCutoff&&!Number.isFinite(e.cnvGainCutoff))throw"cnvGainCutoff is not finite";if(e.cnvLossCutoff&&!Number.isFinite(e.cnvLossCutoff))throw"cnvLossCutoff is not finite";const r=L(e);let o;{const r=await z(e,n.samples,t);r&&(o=new Set(r.map((t=>t.name))))}const i=[],s=[];for(const t of e.rglst)s.push(f.get_lines_bigfile({args:[n.file||n.url,(n.nochr?t.chr.replace("chr",""):t.chr)+":"+t.start+"-"+t.stop],dir:n.dir,callback:n=>{const s=n.split("\t"),a=Number(s[1]),l=Number(s[2]);if(e.cnvMaxLength&&l-a>=e.cnvMaxLength)return;let c;try{c=JSON.parse(s[3])}catch(t){return}if(c.dt==y&&Number.isFinite(c.value)&&!(c.value>0&&e.cnvGainCutoff&&c.value<e.cnvGainCutoff)&&!(c.value<0&&e.cnvLossCutoff&&c.value>e.cnvLossCutoff)&&(c.start=a,c.stop=l,c.class=c.value>0?_:w,(!e.hiddenmclass||!e.hiddenmclass.has(c.class))&&(!c.sample||!o||o.has(c.sample)))){if(c.ssm_id=[t.chr,c.start,c.stop,c.value].join(T),c.sample){const t={sample_id:c.sample};if(c.mattr){if(r)for(const t in r){const e=t in c.mattr?c.mattr[t]:j;if(r[t].has(e))return}e.addFormatValues&&(t.formatK2v=c.mattr)}delete c.sample,c.samples=[t]}i.push(c)}}}));return await Promise.all(s),i}}function J(t,e,n,r,o,i){for(const s of e.yesSamples){if(i&&!i.has(s))continue;n.has(s)||n.set(s,{sample:s});const e=n.get(s);r in e||(e[r]={key:r,values:[],label:r}),o?e[r].values.some((e=>e.dt==t&&e.origin==o))||e[r].values.push({dt:Number.parseInt(t),class:"WT",_SAMPLEID_:s,origin:o}):e[r].values.some((e=>e.dt==t))||e[r].values.push({dt:Number.parseInt(t),class:"WT",_SAMPLEID_:s})}for(const s of e.noSamples){if(i&&!i.has(s))continue;n.has(s)||n.set(s,{sample:s});const e=n.get(s);r in e||(e[r]={key:r,values:[],label:r}),o?e[r].values.some((e=>e.dt==t&&e.origin==o))||e[r].values.push({dt:Number.parseInt(t),class:"Blank",_SAMPLEID_:s,origin:o}):e[r].values.some((e=>e.dt==t))||e[r].values.push({dt:Number.parseInt(t),class:"Blank",_SAMPLEID_:s})}}async function V(t,e){if(t.chr&&Number.isInteger(t.start)&&Number.isInteger(t.stop))return;if(!t.name)throw"both term.name and term.chr/start/stop missing";const n=e.genedb.getjsonbyname.all(t.name);if(0==n.length)throw"unknown gene name";const r=n.find((t=>t.isdefault))||n[0],o=JSON.parse(r.genemodel);if(!o.chr||!Number.isInteger(o.start)||!Number.isInteger(o.stop))throw"invalid chr/start/stop from returned gm";t.chr=o.chr,t.start=o.start,t.stop=o.stop}function Y(t,e){e.yesSamples=new Set,e.noSamples=new Set;const n=`SELECT sample, value\n\t\t\t\tFROM anno_categorical\n\t\t\t\tWHERE term_id = '${e.term_id}'`,r=t.cohort.db.connection.prepare(n).all();for(const t of r)e.yes.value.includes(t.value)?e.yesSamples.add(t.sample):e.no.value.includes(t.value)&&e.noSamples.add(t.sample)}},8089:(t,e,n)=>{"use strict";n.d(e,{f:()=>u});const r=n(9699),o=n(7147),i=n(1017),s=n(2081).spawn,a=n(3856),l=n(334),c=n(9535).snvindelByRangeGetter_bcf;n(1271).run_rust;function u(t){return async(e,n)=>{try{if(!e.query.genome)throw".genome missing";const o=t[e.query.genome];if(!o)throw"invalid genome";const i=function(t,e){const n=t.query;t.get("X-Auth-Token")&&(n.token=t.get("X-Auth-Token"));t.cookies.sessionid&&(n.sessionid=t.cookies.sessionid);n.hiddenmclasslst&&(n.hiddenmclass=new Set(n.hiddenmclasslst.split(",")),delete n.hiddenmclasslst);return n}(e),s=await async function(t,e){if(t.dslabel){if(!e.datasets)throw".datasets{} missing from genome";const n=e.datasets[t.dslabel];if(!n)throw"invalid dslabel";return n}const n={queries:{}};if(t.bcffile||t.bcfurl){const[o,i,s]=r.fileurl({query:{file:t.bcffile,url:t.bcfurl}});if(o)throw o;const a={};s?(a.url=i,a.indexURL=t.bcfindexURL):a.file=i,n.queries.snvindel={byrange:{_tk:a}},n.queries.snvindel.byrange.get=await c(n,e)}return n}(i,o);!function(t,e){var n;if(t.filter0){const n="object"==typeof t.filter0?t.filter0:JSON.parse("string"==typeof t.filter0&&t.filter0.startsWith("%")?decodeURIComponent(t.filter0):t.filter0);t.filter0=e.validate_filter0(n)}t.filterObj&&"string"==typeof t.filterObj&&(t.filterObj=JSON.parse("string"==typeof t.filterObj&&t.filterObj.startsWith("%")?decodeURIComponent(t.filterObj):t.filterObj));if(t.skewerRim){if("format"!=t.skewerRim.type)throw"unknown skewerRim.type";var r,o;if(!t.skewerRim.formatKey)throw"skewerRim.formatKey missing when type=format";if(null===(r=e.queries)||void 0===r||null===(o=r.snvindel)||void 0===o||!o.format)throw"snvindel.format{} not found when type=format";if(!e.queries.snvindel.format[t.skewerRim.formatKey])throw"invalid skewerRim.formatKey";if(t.skewerRim.hiddenvalues=new Set,t.skewerRim.hiddenvaluelst){if(!Array.isArray(t.skewerRim.hiddenvaluelst))throw"query.skewerRim.hiddenvaluelst is not array";for(const e of t.skewerRim.hiddenvaluelst)t.skewerRim.hiddenvalues.add(e);delete t.skewerRim.hiddenvaluelst}}if(t.formatFilter){var i,s;if("object"!=typeof t.formatFilter)throw"formatFilter{} not object";if(null===(i=e.queries)||void 0===i||null===(s=i.snvindel)||void 0===s||!s.format)throw"snvindel.format{} not found when formatFilter is used";const n={};for(const r in t.formatFilter){if(!e.queries.snvindel.format[r])throw"invalid format key from formatFilter";if(!Array.isArray(t.formatFilter[r]))throw"formatFilter[k] value is not array";n[r]=new Set(t.formatFilter[r])}t.formatFilter=n}("format"==(null===(n=t.skewerRim)||void 0===n?void 0:n.type)||t.formatFilter)&&(t.addFormatValues=!0)}(i,s);const a=await async function(t,e){if(t.singleSampleMutation){var n;if(null===(n=e.queries.singleSampleMutation)||void 0===n||!n.get)throw"not supported on this dataset";return{mlst:await e.queries.singleSampleMutation.get(t.singleSampleMutation,t)}}if(t.singleSampleGenomeQuantification){if(!e.queries.singleSampleGenomeQuantification)throw"not supported on this dataset";const n=e.queries.singleSampleGenomeQuantification[t.singleSampleGenomeQuantification.dataType];if(!n)throw"invalid dataType";return await n.get(t.singleSampleGenomeQuantification.sample,t.devicePixelRatio)}if(t.singleSampleGbtk){if(!e.queries.singleSampleGbtk)throw"not supported on this dataset";const n=e.queries.singleSampleGbtk[t.singleSampleGbtk.dataType];if(!n)throw"invalid dataType";return await n.get(t.singleSampleGbtk.sample)}if(t.ssm2canonicalisoform){if(!e.ssm2canonicalisoform)throw"ssm2canonicalisoform not supported on this dataset";return{isoform:await e.ssm2canonicalisoform.get(t)}}if(t.variant2samples){if(!e.variant2samples)throw"not supported by server";return{variant2samples:await e.variant2samples.get(t)}}if(t.m2csq){if(e.queries&&e.queries.snvindel&&e.queries.snvindel.m2csq)return{csq:await e.queries.snvindel.m2csq.get(t)};throw"m2csq not supported on this dataset"}if(t.forTrack){const n={};if(t.skewer){if(n.skewer=[],e.queries.snvindel){const r=await async 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e){t.find((t=>t.chr==n.chr&&t.pos==n.pos&&t.ref==n.ref&&t.alt==n.alt))||(n.groupData=[{refCount:0,altCount:0},{refCount:n._refCount,altCount:n._altCount}],i.push(n))}return i}(i.mlst,s.mlst,t);return{mlst:u,totalSampleCount_group1:a(i.mlst),totalSampleCount_group2:a(s.mlst)}}n.filterObj=c(t);const i=await e.queries.snvindel.byrange.get(n),s=l(i);"filter"==r.type?s.totalSampleCount_group1=a(i):"filter"==(null==o?void 0:o.type)&&(s.totalSampleCount_group2=a(i));return s}(t,n);if(1==t.details.groups.length)u(n,i.mlst,t.details.groups[0]);else{if(2!=t.details.groups.length)throw"q.details.groups.length not 1 or 2";await async function(t,e,n){const[r,i]=e.groups;if("filter"==r.type&&"filter"==i.type)return void await async function(t,e,n){const r=e.groupTestMethods[e.groupTestMethodsIdx];if(!r)throw"details.groupTestMethodsIdx out of bound";switch(r.name){case"Allele frequency difference":return void d(t,e,n);case"Fisher's exact test":return void await m(n);default:throw"unknown value from 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e=t.queries.snvindel.populations.find((t=>t.key==i.key));if(!e)throw"invalid group.key for population";const s=new Map;for(const t of e.sets)s.set(t.key,{ACraw:Number(n.info[t.infokey_AC]||0),ANraw:Number(n.info[t.infokey_AN]||0)});let a=0,l=0;if(i.adjust_race)[a,l]=p(s,r);else for(const t of s.values())l+=t.ACraw,a+=t.ANraw-t.ACraw;o.push({altCount:l,refCount:a})}}else o.push({altCount:n._altCount,refCount:n._refCount});else{if(!i.key)throw"group.key missing for type=info";o.push({value:n.info[i.key]})}return o}function p(t,e){let n=0;for(const e of t.values())n+=e.ANraw;let r=0,o=0;for(const[i,s]of t)s.ANadj=n*e.get(i).average,s.ACadj=0==s.ANadj?0:s.ACraw*s.ANadj/s.ANraw,r+=s.ACadj,o+=s.ANadj;return[o-r,r]}async function m(t){for(let e=0;e<Math.ceil(t.length/200);e++){const n=[];for(let r=200*e;r<200*(e+1);r++){const e=t[r];if(!e)break;const o=e.groupData;o&&o[0]&&o[1]&&Number.isFinite(o[0].altCount)&&Number.isFinite(o[0].refCount)&&Number.isFinite(o[1].altCount)&&Number.isFinite(o[1].refCount)?(n.push({index:r,n1:o[0].altCount,n2:o[0].refCount,n3:Math.floor(o[1].altCount),n4:Math.floor(o[1].refCount)}),e.htmlSections=[{key:"Contigency table",html:`<table style="font-size:.9em">\n\t\t\t\t<tr style="opacity:.5">\n\t\t\t\t <td></td>\n\t\t\t\t <td>Group1</td>\n\t\t\t\t <td>Group 2</td>\n\t\t\t\t</tr>\n\t\t\t\t<tr>\n\t\t\t\t <td style="opacity:.5">ALT allele count</td>\n\t\t\t\t <td>${o[0].altCount}</td>\n\t\t\t\t <td>${Math.floor(o[1].altCount)}</td>\n\t\t\t\t</tr>\n\t\t\t\t<tr>\n\t\t\t\t <td style="opacity:.5">REF allele count</td>\n\t\t\t\t <td>${o[0].refCount}</td>\n\t\t\t\t <td>${Math.floor(o[1].refCount)}</td>\n\t\t\t\t</tr>\n\t\t\t\t<tr>\n\t\t\t\t <td style="opacity:.5">Allele frequency</td>\n\t\t\t\t <td>${(o[0].altCount/(o[0].altCount+o[0].refCount)).toFixed(3)}</td>\n\t\t\t\t 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r=n.slice(0,t).join("."),o=r+"."+n[t];if(o.endsWith("_id")&&!o.endsWith("project_id"))continue;if(o.endsWith("consent_type")||"case.days_to_consent"==o||"case.days_to_index"==o)continue;const i=n[t][0].toUpperCase()+n[t].slice(1).replace(/_/g," "),s={id:o.toLowerCase(),name:i,included_types_set:new Set,child_types_set:new Set};if(t==n.length-1){s.isleaf=!0;const t=d._mapping["ssm_occurrence_centrics."+o];t&&("keyword"==t.type?(s.type="categorical",b++):"long"==t.type?(s.type="integer",s.bins=f[s.id]||JSON.parse(JSON.stringify(u)),_++):"double"==t.type&&(s.type="float",s.bins=f[s.id]||JSON.parse(JSON.stringify(u)),w++)),s.type||v++,h(s)}if(1==t);else if(s.parent_id=r,s.type){s.included_types_set.add(s.type);let t=e.get(r);for(;t&&(t.included_types_set.add(s.type),t.child_types_set.add(s.type),t.parent_id);)t=e.get(t.parent_id)}g.has(o)&&(s.isObjectList=!0),e.set(o,s)}}var k;for(const t of e.values())t.type||x++,t.included_types=[...t.included_types_set],t.child_types=[...t.child_types_set],delete t.included_types_set,delete t.child_types_set;console.log("GDC dictionary:",e.size,"total variables,",y,"lines skipped,",v,"lines with unknown term type,","categorical="+b,"integer="+_,"float="+w,"parent="+x),Object.freeze(e),function(t,e){const n=t.cohort.termdb.q={};async function r(e,n){if(0==e.length||!n)return;const r=await t.termdb.termid2totalsize2.get(e.map((t=>t.id)),JSON.parse(n));for(const t of e)if(t){const e=r.get(t.id);"categorical"==t.type&&e?e.length?t.samplecount=e.map((t=>t[1])).reduce(((t,e)=>t+e)):(t.disabled=!0,t.samplecount=0):"integer"!=t.type&&"float"!=t.type||(t.samplecount=e.total,0==e.total&&(t.disabled=!0))}}n.getRootTerms=async(t,n=null)=>{const o=[];for(const t of e.values())null==t.parent_id&&o.push(JSON.parse(JSON.stringify(t)));return await r(o,n),o},n.getTermChildren=async(t,n=null,o=null)=>{const i=[];for(const n of e.values())n.parent_id==t&&i.push(JSON.parse(JSON.stringify(n)));return await r(i,o),i},n.findTermByName=async(t,n=null,o,s=null,a=null)=>{(t=t.toLowerCase()).includes(" ")&&(t=t.replace(/\s/g,"_"));const l=[];for(const n of e.values())a&&!i(n,a)||n.id.includes(t)&&l.push(JSON.parse(JSON.stringify(n)));return await r(l,s),l},n.getAncestorIDs=t=>{if(!e.has(t))return;const n=t.split("."),r=[];for(let t=1;t<n.length;t++)r.push(n.slice(0,t+1).join("."));return r},n.getAncestorNames=n.getAncestorIDs,n.termjsonByOneid=t=>{const n=e.get(t);return n?JSON.parse(JSON.stringify(n)):null},n.getSupportedChartTypes=()=>{const t={},n={};for(const r of e.values())r.type&&(r.cohort in t||(t[r.cohort]=["barchart","table","regression"],n[r.cohort]=0),"survival"!=r.type||t[r.cohort].includes("survival")||t[r.cohort].push("survival"),"condition"!=r.type||t[r.cohort].includes("cuminc")||t[r.cohort].push("cuminc"),"float"!=r.type&&"integer"!=r.type||(n[r.cohort]+=r.samplecount));for(const e in n)n[e]>0&&t[e].push("boxplot"),n[e]>1&&t[e].push("scatterplot");return t}}(t,e),t.cohort.termdb.termtypeByCohort=[],b&&t.cohort.termdb.termtypeByCohort.push({cohort:"",type:"categorical"}),_&&t.cohort.termdb.termtypeByCohort.push({cohort:"",type:"integer"}),w&&t.cohort.termdb.termtypeByCohort.push({cohort:"",type:"float"}),await async function(t){var e,n,i;const s={"Content-Type":"application/json",Accept:"application/json"},l={filters:{op:"and",content:[{op:"=",content:{field:"access",value:"open"}},{op:"=",content:{field:"data_type",value:"Masked Somatic Mutation"}}]},facets:"cases.project.project_id",size:0},c=await r(o.join(a,"files"),{method:"POST",headers:s,body:JSON.stringify(l)}),u=JSON.parse(c.body);if(t.gdcOpenProjects=new Set,null!=u&&null!==(e=u.data)&&void 0!==e&&null!==(n=e.aggregations)&&void 0!==n&&null!==(i=n["cases.project.project_id"])&&void 0!==i&&i.buckets){for(const e of u.data.aggregations["cases.project.project_id"].buckets)e.key&&t.gdcOpenProjects.add(e.key);console.log("GDC open-access projects:",t.gdcOpenProjects.size)}else console.log("getting open project_id but return is not re.data.aggregations['cases.project.project_id'].buckets")}(t),async function(){try{await p(a+"/ssms"),await p(a+"/ssm_occurrences"),await p(a+"/cases"),await p(a+"/files"),await p(a+"/analysis/top_mutated_genes_by_project"),await async function(t){const e=new Date;try{const e="query termislst2total( $filters: FiltersArgument) {\n\t\texplore {\n\t\t\tcases {\n\t\t\t\taggregations (filters: $filters, aggregations_filter_themselves: true) {\n\t\t\t\t\tprimary_site {buckets { doc_count, key }}\n\t\t\t\t}\n\t\t\t}\n\t\t}}";await r.post(t,{headers:{"Content-Type":"application/json",Accept:"application/json"},body:JSON.stringify({query:e,variables:{}})})}catch(e){throw"gdc api down: "+t}console.log("GDC GraphQL API okay: "+t,new Date-e,"ms")}(l)}catch(t){console.error(`\n##########################################\n#\n# GDC API unavailable\n# ${a}\n# ${l}\n#\n##########################################`)}}(),async function(t){try{if(t.aliquot2submitter={cache:new Map,get:async e=>t.aliquot2submitter.cache.has(e)?t.aliquot2submitter.cache.get(e):e},s.features.stopGdcCacheAliquot)return console.log("GDC aliquot2submitter not cached!");const e=await m(t,1,0);if(!Number.isInteger(e))throw"gdc totalCases not integer";const n=new Date;console.log("Start to cache aliquot IDs of",e,"cases...");const r=1e3;for(let n=0;n<Math.ceil(e/r);n++)await m(t,r,1e3*n);console.log("Done caching",t.aliquot2submitter.cache.size,"aliquot IDs.",new Date-n,"ms")}catch(t){console.log("Error at caching: "+t)}}(t)}function h(t){"case.diagnoses.age_at_diagnosis"!=t.id||(t.printDays2years=!0)}async function p(t){try{const e=new Date;await r(t),console.log("GDC API okay: "+t,new Date-e,"ms")}catch(e){throw"gdc api down: "+t}}async function m(t,e,n,o){var i,s,l;const c=["fields=samples.portions.analytes.aliquots.aliquot_id,samples.submitter_id"];if(o)c.push('filters={"op":"and","content":[{"op":"=","content":{"field":"samples.portions.analytes.aliquots.aliquot_id","value":["'+o+'"]}}]}');else{if(!Number.isInteger(e)||!Number.isInteger(n))throw"size and from not integers";c.push("size="+e),c.push("from="+n)}const u=await r(a+"/cases?"+c.join("&")),f=JSON.parse(u.body);if(!Array.isArray(null==f||null===(i=f.data)||void 0===i?void 0:i.hits))throw"re.data.hits[] not array";for(const e of f.data.hits)if(Array.isArray(e.samples))for(const n of e.samples){const e=n.submitter_id;if(Array.isArray(n.portions))for(const r of n.portions)if(Array.isArray(r.analytes))for(const n of r.analytes)if(Array.isArray(n.aliquots))for(const r of n.aliquots){const n=r.aliquot_id;if(!n)throw"aliquot.aliquot_id missing";t.aliquot2submitter.cache.set(n,e)}}return null===(s=f.data)||void 0===s||null===(l=s.pagination)||void 0===l?void 0:l.total}},7860:(t,e,n)=>{"use strict";n.r(e),n.d(e,{copy_term:()=>N,handle_request_closure:()=>q});var r=n(5684),o=n(7027),i=n(3856),s=n(6191),a=n.n(s),l=n(4065);const c=n(5174),u=n(2852),f=n(5708),d=n(4453),h=n(1468),p=n(8599),m=n(3795),g=n(1711).getOrderedLabels,y=n(1575).isUsableTerm,v=n(2188).uR,b=n(2188).v8,_=n(4603).g,w=n(2974).getData,x=n(601).v,k=n(4143).R;function q(t){return async(e,n)=>{const s=e.query;try{const q=t[s.genome];if(!q)throw"invalid genome";const[A,M]=function(t,e){{const r=t.datasets[e.dslabel];if(r){var n;if(null!=r&&null!==(n=r.cohort)&&void 0!==n&&n.termdb)return[r,r.cohort.termdb];throw".cohort.termdb not found on this dataset"}}if(!t.termdbs)throw"genome-level termdb not available";const r=t.termdbs[e.dslabel];if(!r)throw"invalid dslabel";if(!r.cohort)throw"ds.cohort missing for genome-level termdb";if(!r.cohort.termdb)throw"ds.cohort.termdb{} missing for a genome-level termdb";return[r,r.cohort.termdb]}(q,s);if(s.gettermbyid)return function(t,e,n){const r=n.q.termjsonByOneid(t.gettermbyid);e.send({term:r?N(r):void 0})}(s,n,M);if(s.getcategories)return await async function(t,e,n,r,o){var i,s,a;if(!t.tid)throw".tid missing";const l="geneVariant"==t.type?{name:t.tid,type:"geneVariant",isleaf:!0}:n.q.termjsonByOneid(t.tid),c={filter:t.filter,terms:"geneVariant"==t.type?[{term:l,q:{isAtomic:!0}}]:[{id:t.tid,term:l,q:t.term1_q||S(l,t)}],currentGeneNames:t.currentGeneNames},u=await w(c,r,o);if(u.error)throw u.error;const f=[];if("geneVariant"==t.type){var d;const e=u.samples,n=new Map;if(null!==(d=r.assayAvailability)&&void 0!==d&&d.byDt)for(const[t,e]of Object.entries(r.assayAvailability.byDt))e.byOrigin&&n.set(parseInt(t),{byOrigin:{germline:{},somatic:{}}});for(const[r,o]of Object.entries(e)){const e=o[t.tid].values;for(const t of e){n.has(t.dt)||n.set(t.dt,{});const e=n.get(t.dt);e.byOrigin?e.byOrigin[t.origin][t.class]=e.byOrigin[t.origin][t.class]?e.byOrigin[t.origin][t.class]+1:1:e[t.class]=e[t.class]?e[t.class]+1:1}}for(const[t,e]of n)f.push({dt:t,classes:e})}else{const e=new Map;for(const n in u.samples){const r=u.samples[n][t.tid];r&&("key"in r&&e.set(r.key,1+(e.get(r.key)||0)))}for(const[n,r]of e){var h,p,m,y;f.push({samplecount:r,key:"cox"==(null===(h=t.term1_q)||void 0===h?void 0:h.mode)?JSON.parse(n).event:n,label:"cox"==(null===(p=t.term1_q)||void 0===p?void 0:p.mode)?JSON.parse(n).label:(null==l||null===(m=l.values)||void 0===m||null===(y=m[n])||void 0===y?void 0:y.label)||n})}}const v=g(l,(null===(i=u.refs)||void 0===i||null===(s=i.byTermId)||void 0===s||null===(a=s[t.tid])||void 0===a?void 0:a.bins)||[],t.term1_q);v.length&&f.sort(((t,e)=>v.indexOf(t.label)-v.indexOf(e.label)));e.send({lst:f,orderedLabels:v})}(s,n,M,A,q);if(s.getpercentile)return async function(t,e,n){const r=n.cohort.termdb.q.termjsonByOneid(t.tid);if(!r)throw"invalid termid";if("float"!=r.type&&"integer"!=r.type)throw"not numerical term";const i=t.getpercentile,s=[],a=[],l=await u.get_rows_by_one_key({ds:n,key:t.tid,filter:t.filter?"string"==typeof t.filter?JSON.parse(t.filter):t.filter:null});for(const{value:t}of l)r.values&&r.values[t]&&r.values[t].uncomputable||r.skip0forPercentile&&0==t||a.push(Number(t));for(const t of i){const e=(0,o.Z)(a,t);s.push(e)}e.send({values:s})}(s,n,A);if(s.getdescrstats)return async function(t,e,n){const i=n.cohort.termdb.q.termjsonByOneid(t.tid);if(!i)throw"invalid termid";if("float"!=i.type&&"integer"!=i.type)throw"not numerical term";const s=await u.get_rows_by_one_key({ds:n,key:t.tid,filter:t.filter?"string"==typeof t.filter?JSON.parse(t.filter):t.filter:null}),a=[];for(const{value:e}of s){var l,c;i.values&&i.values[e]&&i.values[e].uncomputable||("log"===(null===(l=t.settings)||void 0===l||null===(c=l.violin)||void 0===c?void 0:c.unit)&&0===e||a.push(Number(e)))}const 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n.q.getRootTerms(r,o)})}(s,n,M);if(s.get_children)return await async function(t,e,n){if(!t.tid)throw"no parent term id";const r=t.cohortValues?t.cohortValues:"",o=t.treeFilter?t.treeFilter:"",i=await n.q.getTermChildren(t.tid,r,o);e.send({lst:i.map(N)})}(s,n,M);if(s.findterm)return await async function(t,e,n,r,o){var i;const s={equals:[],startsWith:[],startsWord:[],includes:[]},a=decodeURIComponent(t.findterm).toUpperCase(),c=y({type:"geneVariant"},t.usecase).has("plot");r.mayGetMatchingGeneNames&&c&&await r.mayGetMatchingGeneNames(s,a,t);const u=[];if(null!==(i=r.queries)&&void 0!==i&&i.defaultBlock2GeneMode&&c){const t=(0,l.getResult)(o,{input:a});if(Array.isArray(t.hits))for(let e=0;e<7&&t.hits[e];e++)u.push({name:t.hits[e],type:"geneVariant"})}"string"!=typeof t.cohortStr&&(t.cohortStr="");const f=await n.q.findTermByName(a,10,t.cohortStr,t.treeFilter,t.usecase,s);u.push(...f.map(N));u.forEach((t=>{"geneVariant"!=t.type&&(t.__ancestors=n.q.getAncestorIDs(t.id),t.__ancestorNames=n.q.getAncestorNames(t.id))})),e.send({lst:u})}(s,n,M,A,q);if(s.getterminfo)return function(t,e,n){if(!t.tid)throw"no term id";e.send({terminfo:n.q.getTermInfo(t.tid)})}(s,n,M);if(s.phewas)return s.update?await f.update_image(s,n):s.getgroup?await f.getgroup(s,n):await f.trigger(s,n,A);if(s.gettermdbconfig)return c.make(s,n,A,q);if(s.getcohortsamplecount)return n.send({count:A.cohort.termdb.q.getcohortsamplecount(s.cohort)});if(s.getsamplecount)return n.send(await async function(t,e,n){const r=a().canDisplaySampleIds(t,n);if("list"==e.getsamplecount){return await u.get_samples(e.filter,n,r)}return await u.get_samplecount(e,n)}(e,s,A));if(s.getsamples)return await async function(t,e,n){const r=(await u.get_samples(t.filter,n)).map((t=>n.cohort.termdb.q.id2sampleName(t)));e.send({samples:r})}(s,n,A);if(s.getcuminc)return await async function(t,e,n){if(!t.minSampleSize)throw"missing minSampleSize";t.minSampleSize=Number(t.minSampleSize);const r=await d.get_incidence(t,n);e.send(r)}(s,n,A);if(s.getsurvival)return await async function(t,e,n){const r=await h.get_survival(t,n);e.send(r)}(s,n,A);if(s.getregression)return await async function(t,e,n){const r=await p.get_regression(t,n);e.send(r)}(s,n,A);if(s.validateSnps)return n.send(await m.validate(s,M,A,q));if(s.getvariantfilter)return function(t,e){var n,r;if(e.track)return void t.send(e.track.variant_filter);t.send((null==e||null===(n=e.queries)||void 0===n||null===(r=n.snvindel)||void 0===r?void 0:r.variant_filter)||{})}(n,A);if(s.getLDdata)return await async function(t,e,n){var r,o;if(!t.ldtkname)throw".ldtkname missing";if(null===(r=e.queries)||void 0===r||null===(o=r.ld)||void 0===o||!o.tracks)throw"no ld tk";const s=e.queries.ld.tracks.find((e=>e.name==t.ldtkname));if(!s)throw"unknown ld tk";if("object"!=typeof t.m)throw"q.m{} not object";if(!t.m.chr)throw"q.m.chr missing";if(!Number.isInteger(t.m.pos))throw"q.m.pos not integer";if(!t.m.ref||!t.m.alt)throw"q.m{} invalid alleles";const a=t.m.ref+"."+t.m.alt,l=(s.nochr?t.m.chr.replace("chr",""):t.m.chr)+":"+t.m.pos+"-"+(t.m.pos+1),c=[];await(0,i.get_lines_bigfile)({args:[s.file,l],dir:s.dir,callback:e=>{const n=e.split("\t"),r=Number.parseInt(n[1]),o=Number.parseInt(n[2]),i=n[3],s=n[4],l=Number.parseFloat(n[5]);r==t.m.pos&&i==a?c.push({pos:o,alleles:s,r2:l}):o==t.m.pos&&s==a&&c.push({pos:r,alleles:i,r2:l})}}),n.send({lst:c})}(s,A,n);if(s.genesetByTermId)return function(t,e,n){if(!n.termMatch2geneSet)throw"this feature is not enabled";if("string"!=typeof t.genesetByTermId||0==t.genesetByTermId.length)throw"invalid query term id";const r=n.q.getGenesetByTermId(t.genesetByTermId);e.send(r)}(s,n,M);if(s.getSampleScatter)return await v(e,s,n,A,q);if(s.getLowessCurve)return await b(e,s,n);if(s.getCohortsData)return await x(s,n,A);if(s.getViolinPlotData)return await _(s,n,A,q);if("mds3queryDetails"==s.for)return function(t,e){const n={},r=e.queries||{};r.snvindel&&(n.snvindel={},r.snvindel.details&&(n.snvindel.details=r.snvindel.details),r.snvindel.populations&&(n.snvindel.populations=r.snvindel.populations));r.trackLst&&(n.trackLst=r.trackLst);if(r.ld){n.ld=JSON.parse(JSON.stringify(r.ld));for(const t of n.ld.tracks)delete t.file}t.send(n)}(n,A);if("termTypes"==s.for)return n.send(await A.getTermTypes(s));if("matrix"==s.for)return await async function(t,e,n,r,o){if(t.getPlotDataByName){if(!r.cohort.matrixplots)throw"ds.cohort.matrixplots missing for the dataset";if(!r.cohort.matrixplots.plots)throw"ds.cohort.matrixplots.plots missing for the dataset";const e=r.cohort.matrixplots.plots.find((e=>e.name===t.getPlotDataByName));if(!e)throw`plot name: q.getPlotDataByName=${getPlotDataByName} missing in ds.cohort.matrixplots.plots`;return void n.send(e.matrixConfig)}const i=await w(t,r,o);if(a().canDisplaySampleIds(e,r))for(const t of Object.values(i.samples))t.sampleName=r.sampleId2Name.get(t.sample);n.send(i)}(s,e,n,A,q);if("mds3variantData"==s.for)return await k(s,n,A,q);throw s.for,"termdb: doesn't know what to do"}catch(t){n.send({error:t.message||t}),t.stack?console.log(t.stack):console.log(t)}}}function N(t){return JSON.parse(JSON.stringify(t))}function S(t,e){if("categorical"==t.type)return{};if("survival"==t.type)return{};if("integer"==t.type||"float"==t.type)return t.bins.default;if("condition"==t.type)return{mode:e.mode,breaks:e.breaks,bar_by_grade:e.bar_by_grade,bar_by_children:e.bar_by_children,value_by_max_grade:e.value_by_max_grade,value_by_most_recent:e.value_by_most_recent,value_by_computable_grade:e.value_by_computable_grade};if("geneVariant"==t.type)return{};throw"unknown term type"}},2974:(t,e,n)=>{"use strict";n.r(e),n.d(e,{getData:()=>f,getSampleData_dictionaryTerms_termdb:()=>d,mayInitiateMatrixplots:()=>h});const r=n(1017),{get_samples:o,get_term_cte:i,interpolateSqlValues:s}=n(2852),{getFilterCTEs:a}=n(5257),l=(n(9157),n(7147),n(7219),n(334)),c=n(3856),{getSampleData_snplstOrLocus:u}=(n(2852),n(8599));async function f(t,e,n){try{return function(t,e,n){if(!e.cohort)throw"cohort missing from ds";if(!t.terms)throw"missing 'terms' parameter";t.ds=e,t.genome=n;for(const e of t.terms)e.term.name||(e.term=t.ds.cohort.termdb.q.termjsonByOneid(e.term.id)),e.q||console.log("do something??");if(t.currentGeneNames&&!Array.isArray(t.currentGeneNames))throw"currentGeneNames[] is not array";t.filter0&&"string"==typeof t.filter0&&(t.filter0=JSON.parse(t.filter0))}(t,e,n),await async function(t){const[e,n]=function(t){const e=[],n=[];for(const r of t){const t=r.term.type;"snplst"==t||"snplocus"==t||"geneVariant"==t?n.push(r):e.push(r)}return[e,n]}(t.terms),{samples:r,refs:i}=await async 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c={};if("linear"==t.regressionType&&(c[n.id]=a.value),"logistic"==t.regressionType&&(c[n.id]=a.key===t.outcome.refGrp?0:1),"cox"==t.regressionType){c[n.timeToEvent.eventId]=a.key;const{age_start:e,age_end:r}=a.value;c[n.timeToEvent.timeId]=r-e,"age"==t.outcome.q.timeScale&&(c[n.timeToEvent.agestartId]=e,c[n.timeToEvent.ageendId]=r)}for(const t of r){const e=s.get(t.id);c[t.id]=e?"numeric"===t.rtype?e.value:e.key:null}o.push(c)}return{regressionType:t.regressionType,binpath:c.binpath,data:o,outcome:n,independent:r}}(t,n);g=(new Date).getTime(),y.NodeJS.makeRinput=(g-m)/1e3+" sec",function(t){const e=t.regressionType,n=t.outcome;if(t.data.length<1)throw"too few samples to fit model";let r=t.independent.length;if("cox"==e)if("time"==n.timeToEvent.timeScale)r+=2;else{if("age"!=n.timeToEvent.timeScale)throw"unknown cox regression time scale";r+=4}else r+=1;if(t.data.find((t=>Object.keys(t).length!=r)))throw"unequal number of variables in data entries";if("logistic"==e){if([...new 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n.independent)e.interactions.includes(t.id)&&(o.interactions||(o.interactions=[]),o.interactions.push(e.id));e.push(o)}if(t.q.restrictAncestry)for(const n of t.q.restrictAncestry.pcs.keys())e.push({id:n,name:n,type:"float",rtype:"numeric"})}function x(t){if("condition"==t.term.type){for(const e of t.q.groups)if(e.name!=t.refGrp)return e;throw"nonref group not found for logistic outcome"}if("predefined-groupset"==t.q.type){if(!t.q.groupsetting)throw"outcome.q.groupsetting{} missing when type=predefined-groupset";if(!Number.isInteger(t.q.groupsetting.predefined_groupset_idx))throw'outcome.q.predefined_groupset_idx not integer when q.type is "predefined-groupset"';if(!t.term.groupsetting)throw"outcome.term.groupsetting missing";const e=t.term.groupsetting.lst[t.q.groupsetting.predefined_groupset_idx];if(!e)throw"groupset not found by outcome.q.predefined_groupset_idx";const n=e.groups.find((e=>e.name!=t.refGrp));if(!n)throw"non-ref group not found for predefined-groupset";return n.name}if("custom-groupset"==t.q.type){if(!t.q.groupsetting)throw"outcome.q.groupsetting{} missing when type=predefined-groupset";if(!t.q.groupsetting.customset)throw"outcome.q.customset missing";const e=t.q.groupsetting.customset.groups.find((e=>e.name!=t.refGrp));if(!e)throw"non-ref group not found for custom-groupset";return e.name}if("values"==t.q.type){if(!t.term.values)throw"outcome.term.values{} missing";for(const e in t.term.values){const n=t.term.values[e];if(n.label!=t.refGrp)return n.label}throw"unknown nonref group from outcome.term.values"}if("custom-bin"==t.q.type){const e=t.q.lst.find((e=>e.label!=t.refGrp));if(!e)throw"non-ref bin is not found for custom-bin";return e.label}if("regular-bin"==t.q.type)throw"do not know a way to find computed bin list for type=regular-bin";throw"unknown outcome.q.type"}async function k(t,e,n,o){m=(new Date).getTime();const i=r.join(c.cachedir,Math.random().toString()+".json");await u.write_file(i,JSON.stringify(t));const f=await s(r.join(c.binpath,"utils","regression.R"),[],[i]);a.unlink(i,(()=>{})),await async function(t,e,n,r,o){if(1!=e.length)throw"expected 1 json line in R output";const i=JSON.parse(e[0]),s=i.data;y["regression.R"]=i.benchmark;for(const e of s){const i={data:{sampleSize:e.data.sampleSize,eventCnt:e.data.eventCnt?e.data.eventCnt:null}};if(e.id){const t=n[e.id];i.id=t;const o=r.independent.find((t=>"snplocus"==t.type));if(!o)throw"snplocus term missing";i.AFstr=o.snpid2AFstr.get(t),i.data.headerRow=N(t,o)}const s=e.data;if(s.residuals&&(i.data.residuals=s.residuals,i.data.residuals.label="linear"==t.regressionType?"Residuals":"Deviance residuals"),"cox"==t.regressionType){if(s.coefficients.rows.length<1)throw"fewer than 1 row in coefficients table"}else if(s.coefficients.rows.length<2)throw"fewer than 2 rows in coefficients table";i.data.coefficients={header:s.coefficients.header,intercept:"cox"==t.regressionType?null:s.coefficients.rows.shift(),terms:{},interactions:[]};for(const t of s.coefficients.rows)if(-1!=t[0].indexOf(":")){const e={},[r,o]=t.shift().split(":"),[s,a]=t.shift().split(":");e.term1=n[r],e.category1=s,e.term2=n[o],e.category2=a,e.lst=t,i.data.coefficients.interactions.push(e)}else{const e=t.shift(),r=t.shift(),o=n[e];i.data.coefficients.terms[o]||(i.data.coefficients.terms[o]={}),r?(i.data.coefficients.terms[o].categories||(i.data.coefficients.terms[o].categories={}),i.data.coefficients.terms[o].categories[r]=t):i.data.coefficients.terms[o].fields=t}i.data.coefficients.label="Coefficients",i.data.type3={header:s.type3.header,terms:{},interactions:[]},"cox"!=t.regressionType&&(i.data.type3.intercept=s.type3.rows.shift());for(const t of s.type3.rows)if(-1!=t[0].indexOf(":")){const e={},[r,o]=t.shift().split(":");e.term1=n[r],e.term2=n[o],e.lst=t,i.data.type3.interactions.push(e)}else{const e=n[t.shift()];i.data.type3.terms[e]||(i.data.type3.terms[e]=t)}if(i.data.type3.label="Type III 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Buffer.from(n).toString("base64"),size:l(t)}),a.unlink(t,(t=>{if(t)throw t}))}s.warnings&&(i.data.warnings=s.warnings);const c=r.independent.find((t=>"snplst"==t.type));if(c){if(c.lowAFsnps&&c.lowAFsnps.size){i.data.warnings||(i.data.warnings=[]);for(const t of c.lowAFsnps.keys())i.data.warnings.push(`${t}: effect allele frequency below cutoff, excluded from analysis`)}if(c.monomorphicLst&&c.monomorphicLst.length){i.data.warnings||(i.data.warnings=[]);for(const t of c.monomorphicLst)i.data.warnings.push(`${t}: monomorphic, excluded from analysis`)}}o.resultLst.push(i)}}(t,f,e,n,o),g=(new Date).getTime(),y.NodeJS.runRegression=(g-m)/1e3+" sec"}async function q(t,e,n,o){const i=t.independent.find((t=>"snplocus"==t.type));if(i){if(m=(new Date).getTime(),function(t,e){for(const n of t.monomorphicLst){const r=t.snpgt2count.get(n),o=[];for(const[t,e]of r)o.push(t+"="+e);const i={id:n,data:{headerRow:N(n,t)}};e.resultLst.push(i)}}(i,o),i.lowAFsnps.size)if("linear"==t.regressionType)await async function(t,e,n,o){const i={},l=new Map;for(const[r,o]of t.lowAFsnps){let t=0,s=null,a=null;const c=[],u=[];for(const{sample:r,noOutcome:i}of e){if(i)continue;const e=n.data[t++].outcome;if(!Number.isFinite(e))continue;const l=o.samples.get(r);if(!l)continue;null==s?s=a=e:(s=Math.min(s,e),a=Math.max(a,e));const[f,d]=l.split("/");f==o.effAle||d==o.effAle?c.push(e):u.push(e)}i[r]={group1values:c,group2values:u},l.set(r,{minv:s,maxv:a})}const f=r.join(c.cachedir,Math.random().toString()+".json");await u.write_file(f,JSON.stringify(i));const d=await s(r.join(c.binpath,"utils/wilcoxon.R"),[],[f]);a.unlink(f,(()=>{}));const p=JSON.parse(d);for(const e in p){const{group1values:n,group2values:r}=i[e],{minv:s,maxv:a}=l.get(e),c=h.boxplot_getvalue(n.sort(((t,e)=>t-e)).map((t=>({value:t}))));c.label=`Carry ${0==t.q.alleleType?"minor":"alternative"} allele, n=${n.length}`;const u=h.boxplot_getvalue(r.sort(((t,e)=>t-e)).map((t=>({value:t}))));u.label=`No ${0==t.q.alleleType?"minor":"alternative"} allele, n=${r.length}`;const f={id:e,AFstr:t.snpid2AFstr.get(e),data:{headerRow:N(e,t),wilcoxon:{pvalue:p[e],boxplots:{minv:s,maxv:a,hasEff:c,noEff:u}}}};o.resultLst.push(f)}}(i,e,n,o);else if("logistic"==t.regressionType)await async function(t,e,n,r){const o=[];let i=0;const s=new Map;for(const[r,a]of t.lowAFsnps){let t=0,l=0,c=0,u=0,f=0;for(const{sample:r,noOutcome:o}of e){if(o)continue;const e=n.data[f++],i="outcome"in e?e.outcome:e.outcome_event;if(0!=i&&1!=i)throw"outcome is not 0 or 1";const s=a.samples.get(r);if(!s)continue;const[d,h]=s.split("/"),p=a.effAle==d||a.effAle==h;0==i?p?l++:t++:p?u++:c++}s.set(i,r);const d={index:i,n1:u,n2:l,n3:c,n4:t};o.push(d),i++}const a=await f("fisher",JSON.stringify({input:o}));for(const e of JSON.parse(a)){const n=s.get(e.index),{effAle:o}=t.lowAFsnps.get(n),i=e.p_value,a="chisq"===e.fisher_chisq,l={id:n,AFstr:t.snpid2AFstr.get(n),data:{headerRow:N(n,t),fisher:{isChi:a,pvalue:Number(i.toFixed(4)),rows:[["","Carry "+o+" allele","No "+o+" allele"],["Have event",e.n1,e.n3],["No event",e.n2,e.n4]]}}};r.resultLst.push(l)}}(i,e,n,o);else{if("cox"!=t.regressionType)throw"unknown regression type";await async function(t,e,n,r){const o={data:{}},i=new Set;for(const[r,s]of t.lowAFsnps){const t=[];let a=0;for(const{sample:r,noOutcome:o}of e){if(o)continue;const e=n.data[a++];if(0!==e.outcome_event&&1!==e.outcome_event)throw"d.outcome_event is not 0/1";if(!Number.isFinite(e.outcome_time))throw"d.outcome_time is not numeric";const i={time:e.outcome_time,event:e.outcome_event},l=s.samples.get(r);if(!l)continue;const[c,u]=l.split("/");i.series=s.effAle==c||s.effAle==u?"1":"2",t.push(i)}new Set(t.map((t=>t.series))).size<2?i.add(r):o.data[r]=t}const s={case:[],tests:{}};let a;await d(o,s);for(const[e,n]of 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0!==a&&a.draftChartTypes&&i[n.cohort].add(...r.features.draftChartTypes),"survival"!=n.type||i[n.cohort].has("survival")||i[n.cohort].add("survival"),"condition"!=n.type||i[n.cohort].has("cuminc")||i[n.cohort].add("cuminc"),"float"!=n.type&&"integer"!=n.type||(s[n.cohort]+=n.samplecount)}}for(const t in s)s[t]>1&&i[t].add("sampleScatter");for(const t in i)i[t]=[...i[t]];if(t.cohort.allowedChartTypes)for(const e in i)i[e]=i[e].filter((e=>t.cohort.allowedChartTypes.includes(e)));if(t.queries){if(t.queries.snvindel||t.queries.trackLst)for(const t in i)i[t].push("genomeBrowser");if(t.queries.geneExpression)for(const t in i)i[t].push("geneExpression")}return i}}function a(t){const e=t.prepare("SELECT name FROM sqlite_master WHERE type='table'").all();return new Set(e.map((t=>t.name)))}function l(t){var e,n;if(t.cohort.termdb.termtypeByCohort){if(!Array.isArray(t.cohort.termdb.termtypeByCohort))throw"termtypeByCohort is not array"}else{if(null===(e=t.cohort)||void 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t.trim().split("\n")){const[t,r]=n.trim().split(/[\s\t]/);if(t&&t.startsWith("rs")){if(e.find((e=>e.rsid==t)))continue;const n={rsid:t,snpid:t};r&&(n.effectAllele=r),e.push(n)}else e.push({rsid:t,snpid:t,invalid:"INVALID RSID"})}return e}(t.snptext);if(!s.length)throw"no snps";await async function(t,e){for(const n of t)if(!n.invalid)if(n.chr&&"string"==typeof n.chr){const t=e.chrlookup[n.chr.toUpperCase()];if(!t){n.invalid=!0;continue}if(!Number.isInteger(n.pos)){n.invalid=!0;continue}if(n.pos<=0||n.pos>=t.len){n.invalid=!0;continue}}else if(n.rsid){const t=await i.query_bigbed_by_name(e.snp.bigbedfile,n.rsid),r=[];for(const n of t){const t=n.split("\t"),o=e.chrlookup[t[0].toUpperCase()];o&&o.major&&r.push(t)}if(0==r.length){n.invalid=!0;continue}const o=r[0];n.chr=o[0],n.pos=Number.parseInt(o[1]),n.dbsnpRef=o[4],n.dbsnpAlts=o[6].split(",").filter(Boolean)}else n.invalid=!0;if(!t.find((t=>!t.invalid)))throw"no valid variants"}(s,n);const l=await async function(t,e,n){let s;if(n.track){if(s=n.track.vcf,!s)throw"ds.track.vcf missing"}else s=n.queries.snvindel.byrange._tk;const l=new Set,u=[];for(const t of e){if(t.invalid)continue;let e;var f;if(s.chr2files){if(e=null===(f=s.chr2files)||void 0===f?void 0:f[t.chr].file,!e)throw"chr not in chr2files"}else if(s.chr2bcffile){if(e=s.chr2bcffile[t.chr],!e)throw"chr not in chr2bcffile"}else e=s.file||s.url;l.add(e);const n=(s.nochr?t.chr.replace("chr",""):t.chr)+"\t"+(t.pos+1);u.push(n)}const d=o.join(a.cachedir,await i.write_tmpfile(u.join("\n"))),h=o.join(a.cachedir,await i.write_tmpfile([...l].join("\n")));await i.get_lines_bigfile({isbcf:!0,args:["query","-R",d,"-f",c,"-v",h],dir:s.dir,callback:t=>{const n=t.split("\t"),r=(s.nochr?"chr":"")+n[0],o=n[1],i=n[2],a=n[3].split(","),l=e.find((t=>{if(t.chr==r&&t.pos===o-1&&t.dbsnpRef==i&&t.dbsnpAlts.some((t=>a.includes(t))))return t}));if(l){l.referenceAllele=i,l.altAlleles=a,l.gtlst=[];for(let t=4;t<n.length;t++)l.gtlst.push("."==n[t]?"":n[t])}}}),r.unlink(d,(()=>{})),r.unlink(h,(()=>{}));const p=["snpid\tchr\tpos\tref\talt\teff\t"+s.samples.map((t=>t.name)).join("\t")];for(const t of e)t.invalid||t.gtlst&&(p.push(t.snpid+"\t"+t.chr+"\t"+t.pos+"\t"+t.referenceAllele+"\t"+t.altAlleles.join(",")+"\t"+(t.effectAllele||"")+"\t"+t.gtlst.join("\t")),delete t.gtlst);const m=t.genome+"_"+t.dslabel+"_"+new Date/1+"_"+Math.ceil(1e4*Math.random());return await i.write_file(o.join(a.cache_snpgt.dir,m),p.join("\n")),m}(t,s,e);return{snps:s,cacheid:l}}(t,n,d);if(t.chr)return await async function(t,e,n){const r=Number(t.start),s=Number(t.stop);if(!Number.isInteger(r)||!Number.isInteger(s))throw"start/stop are not integers";if(r>s||r<0)throw"invalid start/stop coordinate";let c,d;if(e.track){if(c=e.track.vcf,!c)throw"ds.track.vcf missing";if(d=c.chr2bcffile[t.chr],!d)throw"chr not in chr2bcffile"}else{var p;if(c=e.queries.snvindel.byrange._tk,c.chr2files)d=null===(p=c.chr2files)||void 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as key, value\n\t\t\tFROM precomputed_chc_grade\n\t\t\tWHERE\n\t\t\t\tterm_id=?\n\t\t\t\tAND ${i}=1\n\t\t\t\tAND value IN (${t.values.map((t=>"?")).join(",")})\n\t\t`),r.push(t.name,e.id,...t.values.map((t=>t.toString())));return{sql:`${t} AS (\n\t\t\t${s.join("\nUNION ALL\n")}\n\t\t)`,tablename:t}}},2852:(t,e,n)=>{"use strict";n.r(e),n.d(e,{getUncomputableClause:()=>v,get_bins:()=>_,get_numericMinMaxPct:()=>x,get_numericsummary:()=>w,get_rows:()=>p,get_rows_by_one_key:()=>h,get_samplecount:()=>f,get_samples:()=>u,get_summary:()=>g,get_summary_numericcategories:()=>d,get_term_cte:()=>m,interpolateSqlValues:()=>k});const r=n(9699),o=n(4048),i=n(5257).getFilterCTEs,s=n(827),a=n(2747),l=n(9723),c=n(610).s;n(334);async function u(t,e,n=!1){const r=await i(t,e),o=e.cohort.db.connection.prepare(r?`WITH ${r.filters} SELECT sample as id, name FROM ${r.CTEname} join sampleidmap on sample = sampleidmap.id`:"SELECT id, name FROM sampleidmap");let s;if(s=r?o.all(r.values):o.all(),n)return s;for(const t of s)delete t.name;return s}async function f(t,e){if(!t.filter)throw"filter missing";let n;if("object"==typeof t.filter)n=t.filter;else{if("string"!=typeof t.filter)throw"q.filter not obj or str";n=JSON.parse(t.filter)}const r=await i(n,e),o=`WITH ${r.filters}\n\t\tSELECT 'FILTERED_COHORT' as subcohort, count(distinct sample) as samplecount \n\t\tFROM ${r.CTEname}`;return e.cohort.db.connection.prepare(o).all(r.values)}async function d(t){const e=t.ds.cohort.termdb.q.termjsonByOneid(t.term_id);if("integer"!=e.type&&"float"!=e.type)throw"term is not numeric";if(!e.values)return[];const n=await i(t.filter,t.ds),r=n?n.values.slice():[];r.push(t.term_id);const o=[];for(const t in e.values)o.push("?"),r.push(Number(t));const s=`\n\t\t${n?"WITH "+n.filters:""}\n\t\tSELECT count(sample) AS samplecount,value\n\t\tFROM anno_${e.type}\n\t\tWHERE term_id=?\n\t\t${n?"AND sample IN "+n.CTEname:""}\n\t\tAND value IN (${o.join(",")})\n\t\tGROUP BY value`;return t.ds.cohort.db.connection.prepare(s).all(r)}async function h(t){if(!t.key)throw".key missing";if(!t.ds)throw".ds{} missing";const e=await i(t.filter,t.ds),n=e?e.values.slice():[],r=t.ds.cohort.termdb.q.termjsonByOneid(t.key);n.push(t.key);const o=`\n\t\t${e?"WITH "+e.filters:""}\n\t\tSELECT sample, value\n\t\tFROM anno_${r.type}\n\t\tWHERE term_id=?\n\t\t${e?" AND sample IN "+e.CTEname:""}`;return t.ds.cohort.db.connection.prepare(o).all(n)}async function p(t,e={}){"string"==typeof t.filter&&(t.filter=JSON.parse(decodeURIComponent(t.filter)));const n=Object.assign({withCTEs:!0,columnas:"t1.sample AS sample",groupby:""},e),r=await i(t.filter,t.ds),o=r?r.values.slice():[],s=await m(t,o,0,r),a=await m(t,o,1,r),l=await m(t,o,2,r),c=[s,a,l].map(((t,e)=>`\n\t\tSELECT sample, key, value, ${e} as termNum\n\t\tFROM ${t.tablename}\n\t\t${r?"WHERE sample IN "+r.CTEname:""}\n\t`)).join("\nUNION ALL\n"),u=`WITH\n\t\t${r?r.filters+",":""}\n\t\t${s.sql},\n\t\t${a.sql},\n\t\t${l.sql}\n\t\t${c}`;try{const e=t.ds.cohort.db.connection.prepare(u).all(o),i=new Map;for(const t of e){i.has(t.sample)||i.set(t.sample,{sample:t.sample});const e=i.get(t.sample),n=`key${t.termNum}`;n in e||(e[n]=[]),e[n].push(t)}const c=[],f=new Map;for(const e of i.values())if("key1"in e){if(t.term0_q&&t.term0_id){if(!("key0"in e))continue}else e.key0=[{key:"",value:""}];if(t.term2_q&&(t.term2_id||"samplelst"===t.term2.type)){if(!("key2"in e))continue}else e.key2=[{key:"",value:""}];e.rows=[];for(const t of e.key0)for(const n of e.key1)for(const r of e.key2)e.rows.push({sample:e.sample,key0:t.key,val0:t.value,key1:n.key,val1:n.value,key2:r.key,val2:r.value});for(const t of e.rows)if(n.groupby){if(!f.has(t[n.groupby])){const e=Object.assign({samplecount:0},t);c.push(e),f.set(t[n.groupby],e)}f.get(t[n.groupby]).samplecount++}else c.push(t)}return n.withCTEs?{lst:c,CTE0:s,CTE1:a,CTE2:l,filter:r}:c}catch(t){throw console.log("error in sql:\n",k(u,o)),t}}async function m(t,e,n,r,o=null){const i=o&&o.term||t[`term${n}`],u=i?i.id:t["term"+n+"_id"];if("samplelst"!=(null==i?void 0:i.type))if(o||1!=n){if(!u){const t="samplekey_"+n;return{tablename:t,sql:`${t} AS (\nSELECT null AS sample, '' as key, '' as value\n)`}}}else if(!u)throw"missing term1 id";const f=i&&i.type?i:t.ds.cohort.termdb.q.termjsonByOneid(u);if(!f)throw`no term found by id='${u}'`;let d=o&&o.q||t["term"+n+"_q"]||{};"string"==typeof d&&(d=JSON.parse(decodeURIComponent(d)));const h="samplekey_"+n;let p;if("categorical"==f.type){const n=b(f,d);p=await a[n?"groupset":"values"].getCTE(h,f,t.ds,d,e,n)}else if("integer"==f.type||"float"==f.type){const o="spline"==d.mode?"cubicSpline":d.mode||"discrete";p=await s[o].getCTE(h,f,t.ds,d,e,n,r)}else if("condition"==f.type){const n=d.mode||"discrete";p=await l[n].getCTE(h,f,t.ds,d,e)}else if("survival"==f.type)p=function(t,e,n,r,o){return r.push(e.id),{sql:`${t} AS (\n\t\t\tSELECT sample, exit_code as key, tte AS value\n\t\t\tFROM survival s\n\t\t\tWHERE s.term_id=?\n\t\t\t${o?"AND s.sample IN "+o.CTEname:""}\n\t\t)`,tablename:t}}(h,f,0,e,r);else{if("samplelst"!=f.type)throw"unknown term type";p=await c.getCTE(h,o||{term:f,q:d},e)}return p}async function g(t){const e=await p(t,{withCTEs:!0,groupby:"key1"}),n=[0,1,2],r={};for(const o of n)r[o]=y(t,o,e);for(const t of e.lst)for(const e of n)r[e](t);return e}function y(t,e,n){const r="key"+e,o="val"+e,i=t=>{delete t[r],delete t[o]},s=t["term"+e+"_id"];if(!s)return i;const a=t.ds.cohort.termdb.q.termjsonByOneid(s);if(!a)return i;const l=1!=e||t.term0_id||t.term2_id?r:"key",c=1!=e||t.term0_id||t.term2_id?r:"label";if("integer"==a.type||"float"==a.type){const i=n["CTE"+e],s="range"+(1!=e||t.term0_id||t.term2_id?e:"");return t=>{t[s]=i.name2bin.get(t[r]),t[c]=t[r],delete t[o],l!==r&&(t[l]=t[r],delete t[r])}}{const n=t["term"+e+"_q"];return e=>{e[c]=function(t,e,n,r){if("categorical"==e.type)return e.values&&t in e.values?e.values[t].label:t;if("condition"==e.type){var o;if(0==(null===(o=n.breaks)||void 0===o?void 0:o.length)){if(!(t in e.values))throw`unknown grade='${t}'`;return e.values[t].label}return t}if(e.values)return t in e.values?e.values[t].label:t;if("integer"==e.type||"float"==e.type)throw"should not work for numeric term";throw"unknown term type"}(e[r],a,n,t.ds),delete e[o],l!==r&&(e[l]=e[r],delete e[r])}}}function v(t,e,n=""){if(!t.values||!e.computableValuesOnly)return{values:[],clause:""};const r=Object.keys(t.values).filter((e=>t.values[e].uncomputable)),o=n?`${n}.value`:"value";return{values:r,clause:r.length?`AND ${o} NOT IN (${r.map((()=>"?")).join(",")})`:""}}function b(t,e){if(e.groupsetting&&!e.groupsetting.disabled&&e.groupsetting.inuse){if(Number.isInteger(e.groupsetting.predefined_groupset_idx)){if(e.groupsetting.predefined_groupset_idx<0)throw"q.predefined_groupset_idx out of bound";if(!t.groupsetting)throw"term.groupsetting missing when q.predefined_groupset_idx in use";if(!t.groupsetting.lst)throw"term.groupsetting.lst missing when q.predefined_groupset_idx in use";const n=t.groupsetting.lst[e.groupsetting.predefined_groupset_idx];if(!n)throw"q.predefined_groupset_idx out of bound";return n}if(e.groupsetting.customset)return e.groupsetting.customset;throw"do not know how to get groupset"}}function _(t,e,n,r,i){if("continuous"!=t.mode&&"spline"!=t.mode)return o.compute_bins(t,(t=>x(n,e,i,t)))}async function w(t,e,n,o=!1){const s="string"==typeof t.filter?JSON.parse(decodeURIComponent(t.filter)):t.filter;"integer"!=e.type&&"float"!=e.type||a.lst.find((t=>t.term.id==e.id&&"ranges"in t))||a.lst.push({type:"tvs",tvs:{term:e,ranges:_(t,e,n)}});const a=await i(s,n),l=[];a&&l.push(...a.values);const c=e.values?Object.keys(e.values).filter((t=>e.values[t].uncomputable)):[],u=`${a?"WITH "+a.filters+" ":""}\n\t\tSELECT value\n\t\tFROM anno_${e.type}\n\t\tWHERE\n\t\t${a?"sample IN "+a.CTEname+" AND ":""}\n\t\tterm_id=?\n\t\t${c.length?"AND value NOT IN ("+c.join(",")+")":""}`;l.push(e.id);const f=n.cohort.db.connection.prepare(u).all(l);if(!f.length)return null;f.sort(((t,e)=>t.value-e.value));const d=r.boxplot_getvalue(f);d.mean=f.length?f.reduce(((t,e)=>t+e.value),0)/f.length:0;let h=0;for(const t of f)h+=Math.pow(t.value-d.mean,2);return d.sd=Math.sqrt(h/(f.length-1)),d.min=f[0].value,d.max=f[f.length-1].value,o&&(d.values=f.map((t=>t.value))),d}function x(t,e,n,r=[]){const o=[];n&&o.push(...n.values),o.push(e.id);const i=e.values?Object.keys(e.values).filter((t=>e.values[t].uncomputable)):[],s=[],a=[],l=[];let c;for(const t of r)c="pct_"+t,s.push(`\n\t\t${c} AS (\n\t\t SELECT value\n\t\t FROM vals\n\t\t LIMIT 1\n\t\t OFFSET (\n\t\t SELECT cast ( x as int ) - ( x < cast ( x as int ))\n\t\t FROM (\n\t\t SELECT cast(?*pct as int) as x \n\t\t FROM p\n\t\t )\n\t\t )\n\t\t)`),o.push(t),a.push(c),l.push(`${c}.value AS ${"p"+t}`);const u=`WITH\n\t\t${n?n.filters+", ":""} \n\t\tvals AS (\n\t\t\tSELECT value\n\t\t\tFROM anno_${e.type}\n\t\t\tWHERE\n\t\t\t${n?"sample IN "+n.CTEname+" AND ":""}\n\t\t\tterm_id=?\n\t\t\t${i.length?"AND value NOT IN ("+i.join(",")+")":""}\n\t\t\tORDER BY value ASC\n\t\t),\n\t\tp AS (\n\t\t\tSELECT count(value)/100 as pct\n\t\t\tFROM vals\n\t\t)\n\t\t${s.length?",\n"+s.join(","):""}\n\t\tSELECT 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l)!("name"in t)&&t.label&&(t.name=t.label),u.set(t.name,t),c.push(`SELECT '${t.name}' AS name,\n\t\t\t\t${null==t.start?0:t.start} AS start,\n\t\t\t\t${null==t.stop?0:t.stop} AS stop,\n\t\t\t\t0 AS unannotated,\n\t\t\t\t${t.startunbounded?1:0} AS startunbounded,\n\t\t\t\t${t.stopunbounded?1:0} AS stopunbounded,\n\t\t\t\t${t.startinclusive?1:0} AS startinclusive,\n\t\t\t\t${t.stopinclusive?1:0} AS stopinclusive`);const f=[];if(e.values)for(const t in e.values){const n=e.values[t].uncomputable;if(o.computableValuesOnly&&n)continue;if(!o.computableValuesOnly&&!n)continue;f.push(t);const r=e.values[t];c.push(`SELECT '${r.label}' AS name,\n\t ${t} AS start,\n\t 0 AS stop,\n\t 1 AS unannotated,\n\t 0 AS startunbounded,\n\t 0 AS stopunbounded,\n\t 0 AS startinclusive,\n\t 0 AS stopinclusive`),u.set(r.label,{is_unannotated:!0,value:t,label:r.label})}const d="bin_defs_"+s,h=(0,r.getUncomputableClause)(e,o,"a");i.push(...h.values);return{sql:`${d} AS (\n\t\t\t\t${c.join("\nUNION 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i}_link(t,e){this._halfedges[t]=e,-1!==e&&(this._halfedges[e]=t)}_addTriangle(t,e,n,r,o,i){const s=this.trianglesLen;return this._triangles[s]=t,this._triangles[s+1]=e,this._triangles[s+2]=n,this._link(s,r),this._link(s+1,o),this._link(s+2,i),this.trianglesLen+=3,s}}function Kr(t,e,n,r){const o=t-n,i=e-r;return o*o+i*i}function Xr(t,e,n,r,o,i,s,a){const l=t-s,c=e-a,u=n-s,f=r-a,d=o-s,h=i-a,p=u*u+f*f,m=d*d+h*h;return l*(f*m-p*h)-c*(u*m-p*d)+(l*l+c*c)*(u*h-f*d)<0}function to(t,e,n,r,o,i){const s=n-t,a=r-e,l=o-t,c=i-e,u=s*s+a*a,f=l*l+c*c,d=.5/(s*c-a*l),h=(c*u-a*f)*d,p=(s*f-l*u)*d;return h*h+p*p}function eo(t,e,n,r){if(r-n<=20)for(let o=n+1;o<=r;o++){const r=t[o],i=e[r];let s=o-1;for(;s>=n&&e[t[s]]>i;)t[s+1]=t[s--];t[s+1]=r}else{let o=n+1,i=r;no(t,n+r>>1,o),e[t[n]]>e[t[r]]&&no(t,n,r),e[t[o]]>e[t[r]]&&no(t,o,r),e[t[n]]>e[t[o]]&&no(t,n,o);const s=t[o],a=e[s];for(;;){do{o++}while(e[t[o]]<a);do{i--}while(e[t[i]]>a);if(i<o)break;no(t,o,i)}t[n+1]=t[i],t[i]=s,r-o+1>=i-n?(eo(t,e,o,r),eo(t,e,n,i-1)):(eo(t,e,n,i-1),eo(t,e,o,r))}}function no(t,e,n){const r=t[e];t[e]=t[n],t[n]=r}function ro(t){return t[0]}function oo(t){return t[1]}const io=1e-6;class so{constructor(){this._x0=this._y0=this._x1=this._y1=null,this._=""}moveTo(t,e){this._+=`M${this._x0=this._x1=+t},${this._y0=this._y1=+e}`}closePath(){null!==this._x1&&(this._x1=this._x0,this._y1=this._y0,this._+="Z")}lineTo(t,e){this._+=`L${this._x1=+t},${this._y1=+e}`}arc(t,e,n){const r=(t=+t)+(n=+n),o=e=+e;if(n<0)throw new Error("negative radius");null===this._x1?this._+=`M${r},${o}`:(Math.abs(this._x1-r)>io||Math.abs(this._y1-o)>io)&&(this._+="L"+r+","+o),n&&(this._+=`A${n},${n},0,1,1,${t-n},${e}A${n},${n},0,1,1,${this._x1=r},${this._y1=o}`)}rect(t,e,n,r){this._+=`M${this._x0=this._x1=+t},${this._y0=this._y1=+e}h${+n}v${+r}h${-n}Z`}value(){return this._||null}}class ao{constructor(){this._=[]}moveTo(t,e){this._.push([t,e])}closePath(){this._.push(this._[0].slice())}lineTo(t,e){this._.push([t,e])}value(){return this._.length?this._:null}}class lo{constructor(t,[e,n,r,o]=[0,0,960,500]){if(!((r=+r)>=(e=+e)&&(o=+o)>=(n=+n)))throw new Error("invalid bounds");this.delaunay=t,this._circumcenters=new Float64Array(2*t.points.length),this.vectors=new Float64Array(2*t.points.length),this.xmax=r,this.xmin=e,this.ymax=o,this.ymin=n,this._init()}update(){return this.delaunay.update(),this._init(),this}_init(){const{delaunay:{points:t,hull:e,triangles:n},vectors:r}=this,o=this.circumcenters=this._circumcenters.subarray(0,n.length/3*2);for(let e,r,i=0,s=0,a=n.length;i<a;i+=3,s+=2){const a=2*n[i],l=2*n[i+1],c=2*n[i+2],u=t[a],f=t[a+1],d=t[l],h=t[l+1],p=t[c],m=t[c+1],g=d-u,y=h-f,v=p-u,b=m-f,_=2*(g*b-y*v);if(Math.abs(_)<1e-9){let o=1e9;const i=2*n[0];o*=Math.sign((t[i]-u)*b-(t[i+1]-f)*v),e=(u+p)/2-o*b,r=(f+m)/2+o*v}else{const t=1/_,n=g*g+y*y,o=v*v+b*b;e=u+(b*n-y*o)*t,r=f+(g*o-v*n)*t}o[s]=e,o[s+1]=r}let i,s,a,l=e[e.length-1],c=4*l,u=t[2*l],f=t[2*l+1];r.fill(0);for(let n=0;n<e.length;++n)l=e[n],i=c,s=u,a=f,c=4*l,u=t[2*l],f=t[2*l+1],r[i+2]=r[c]=a-f,r[i+3]=r[c+1]=u-s}render(t){const e=null==t?t=new so:void 0,{delaunay:{halfedges:n,inedges:r,hull:o},circumcenters:i,vectors:s}=this;if(o.length<=1)return null;for(let e=0,r=n.length;e<r;++e){const r=n[e];if(r<e)continue;const o=2*Math.floor(e/3),s=2*Math.floor(r/3),a=i[o],l=i[o+1],c=i[s],u=i[s+1];this._renderSegment(a,l,c,u,t)}let a,l=o[o.length-1];for(let e=0;e<o.length;++e){a=l,l=o[e];const n=2*Math.floor(r[l]/3),c=i[n],u=i[n+1],f=4*a,d=this._project(c,u,s[f+2],s[f+3]);d&&this._renderSegment(c,u,d[0],d[1],t)}return e&&e.value()}renderBounds(t){const e=null==t?t=new so:void 0;return t.rect(this.xmin,this.ymin,this.xmax-this.xmin,this.ymax-this.ymin),e&&e.value()}renderCell(t,e){const n=null==e?e=new so:void 0,r=this._clip(t);if(null===r||!r.length)return;e.moveTo(r[0],r[1]);let o=r.length;for(;r[0]===r[o-2]&&r[1]===r[o-1]&&o>1;)o-=2;for(let t=2;t<o;t+=2)r[t]===r[t-2]&&r[t+1]===r[t-1]||e.lineTo(r[t],r[t+1]);return e.closePath(),n&&n.value()}*cellPolygons(){const{delaunay:{points:t}}=this;for(let e=0,n=t.length/2;e<n;++e){const t=this.cellPolygon(e);t&&(t.index=e,yield t)}}cellPolygon(t){const e=new ao;return this.renderCell(t,e),e.value()}_renderSegment(t,e,n,r,o){let i;const s=this._regioncode(t,e),a=this._regioncode(n,r);0===s&&0===a?(o.moveTo(t,e),o.lineTo(n,r)):(i=this._clipSegment(t,e,n,r,s,a))&&(o.moveTo(i[0],i[1]),o.lineTo(i[2],i[3]))}contains(t,e,n){return(e=+e)==e&&(n=+n)==n&&this.delaunay._step(t,e,n)===t}*neighbors(t){const e=this._clip(t);if(e)for(const n of this.delaunay.neighbors(t)){const t=this._clip(n);if(t)t:for(let r=0,o=e.length;r<o;r+=2)for(let i=0,s=t.length;i<s;i+=2)if(e[r]==t[i]&&e[r+1]==t[i+1]&&e[(r+2)%o]==t[(i+s-2)%s]&&e[(r+3)%o]==t[(i+s-1)%s]){yield n;break t}}}_cell(t){const{circumcenters:e,delaunay:{inedges:n,halfedges:r,triangles:o}}=this,i=n[t];if(-1===i)return null;const s=[];let a=i;do{const n=Math.floor(a/3);if(s.push(e[2*n],e[2*n+1]),a=a%3==2?a-2:a+1,o[a]!==t)break;a=r[a]}while(a!==i&&-1!==a);return s}_clip(t){if(0===t&&1===this.delaunay.hull.length)return[this.xmax,this.ymin,this.xmax,this.ymax,this.xmin,this.ymax,this.xmin,this.ymin];const e=this._cell(t);if(null===e)return null;const{vectors:n}=this,r=4*t;return n[r]||n[r+1]?this._clipInfinite(t,e,n[r],n[r+1],n[r+2],n[r+3]):this._clipFinite(t,e)}_clipFinite(t,e){const n=e.length;let r,o,i,s,a=null,l=e[n-2],c=e[n-1],u=this._regioncode(l,c),f=0;for(let d=0;d<n;d+=2)if(r=l,o=c,l=e[d],c=e[d+1],i=u,u=this._regioncode(l,c),0===i&&0===u)s=f,f=0,a?a.push(l,c):a=[l,c];else{let e,n,d,h,p;if(0===i){if(null===(e=this._clipSegment(r,o,l,c,i,u)))continue;[n,d,h,p]=e}else{if(null===(e=this._clipSegment(l,c,r,o,u,i)))continue;[h,p,n,d]=e,s=f,f=this._edgecode(n,d),s&&f&&this._edge(t,s,f,a,a.length),a?a.push(n,d):a=[n,d]}s=f,f=this._edgecode(h,p),s&&f&&this._edge(t,s,f,a,a.length),a?a.push(h,p):a=[h,p]}if(a)s=f,f=this._edgecode(a[0],a[1]),s&&f&&this._edge(t,s,f,a,a.length);else if(this.contains(t,(this.xmin+this.xmax)/2,(this.ymin+this.ymax)/2))return[this.xmax,this.ymin,this.xmax,this.ymax,this.xmin,this.ymax,this.xmin,this.ymin];return a}_clipSegment(t,e,n,r,o,i){for(;;){if(0===o&&0===i)return[t,e,n,r];if(o&i)return null;let s,a,l=o||i;8&l?(s=t+(n-t)*(this.ymax-e)/(r-e),a=this.ymax):4&l?(s=t+(n-t)*(this.ymin-e)/(r-e),a=this.ymin):2&l?(a=e+(r-e)*(this.xmax-t)/(n-t),s=this.xmax):(a=e+(r-e)*(this.xmin-t)/(n-t),s=this.xmin),o?(t=s,e=a,o=this._regioncode(t,e)):(n=s,r=a,i=this._regioncode(n,r))}}_clipInfinite(t,e,n,r,o,i){let s,a=Array.from(e);if((s=this._project(a[0],a[1],n,r))&&a.unshift(s[0],s[1]),(s=this._project(a[a.length-2],a[a.length-1],o,i))&&a.push(s[0],s[1]),a=this._clipFinite(t,a))for(let e,n=0,r=a.length,o=this._edgecode(a[r-2],a[r-1]);n<r;n+=2)e=o,o=this._edgecode(a[n],a[n+1]),e&&o&&(n=this._edge(t,e,o,a,n),r=a.length);else this.contains(t,(this.xmin+this.xmax)/2,(this.ymin+this.ymax)/2)&&(a=[this.xmin,this.ymin,this.xmax,this.ymin,this.xmax,this.ymax,this.xmin,this.ymax]);return a}_edge(t,e,n,r,o){for(;e!==n;){let n,i;switch(e){case 5:e=4;continue;case 4:e=6,n=this.xmax,i=this.ymin;break;case 6:e=2;continue;case 2:e=10,n=this.xmax,i=this.ymax;break;case 10:e=8;continue;case 8:e=9,n=this.xmin,i=this.ymax;break;case 9:e=1;continue;case 1:e=5,n=this.xmin,i=this.ymin}r[o]===n&&r[o+1]===i||!this.contains(t,n,i)||(r.splice(o,0,n,i),o+=2)}if(r.length>4)for(let t=0;t<r.length;t+=2){const e=(t+2)%r.length,n=(t+4)%r.length;(r[t]===r[e]&&r[e]===r[n]||r[t+1]===r[e+1]&&r[e+1]===r[n+1])&&(r.splice(e,2),t-=2)}return o}_project(t,e,n,r){let o,i,s,a=1/0;if(r<0){if(e<=this.ymin)return null;(o=(this.ymin-e)/r)<a&&(s=this.ymin,i=t+(a=o)*n)}else if(r>0){if(e>=this.ymax)return null;(o=(this.ymax-e)/r)<a&&(s=this.ymax,i=t+(a=o)*n)}if(n>0){if(t>=this.xmax)return null;(o=(this.xmax-t)/n)<a&&(i=this.xmax,s=e+(a=o)*r)}else if(n<0){if(t<=this.xmin)return null;(o=(this.xmin-t)/n)<a&&(i=this.xmin,s=e+(a=o)*r)}return[i,s]}_edgecode(t,e){return(t===this.xmin?1:t===this.xmax?2:0)|(e===this.ymin?4:e===this.ymax?8:0)}_regioncode(t,e){return(t<this.xmin?1:t>this.xmax?2:0)|(e<this.ymin?4:e>this.ymax?8:0)}}const co=2*Math.PI,uo=Math.pow;function fo(t){return t[0]}function ho(t){return t[1]}function po(t,e,n){return[t+Math.sin(t+e)*n,e+Math.cos(t-e)*n]}class mo{static from(t,e=fo,n=ho,r){return new mo("length"in t?function(t,e,n,r){const o=t.length,i=new Float64Array(2*o);for(let s=0;s<o;++s){const o=t[s];i[2*s]=e.call(r,o,s,t),i[2*s+1]=n.call(r,o,s,t)}return i}(t,e,n,r):Float64Array.from(function*(t,e,n,r){let o=0;for(const i of t)yield e.call(r,i,o,t),yield n.call(r,i,o,t),++o}(t,e,n,r)))}constructor(t){this._delaunator=new Qr(t),this.inedges=new Int32Array(t.length/2),this._hullIndex=new Int32Array(t.length/2),this.points=this._delaunator.coords,this._init()}update(){return this._delaunator.update(),this._init(),this}_init(){const t=this._delaunator,e=this.points;if(t.hull&&t.hull.length>2&&function(t){const{triangles:e,coords:n}=t;for(let t=0;t<e.length;t+=3){const r=2*e[t],o=2*e[t+1],i=2*e[t+2];if((n[i]-n[r])*(n[o+1]-n[r+1])-(n[o]-n[r])*(n[i+1]-n[r+1])>1e-10)return!1}return!0}(t)){this.collinear=Int32Array.from({length:e.length/2},((t,e)=>e)).sort(((t,n)=>e[2*t]-e[2*n]||e[2*t+1]-e[2*n+1]));const t=this.collinear[0],n=this.collinear[this.collinear.length-1],r=[e[2*t],e[2*t+1],e[2*n],e[2*n+1]],o=1e-8*Math.hypot(r[3]-r[1],r[2]-r[0]);for(let t=0,n=e.length/2;t<n;++t){const n=po(e[2*t],e[2*t+1],o);e[2*t]=n[0],e[2*t+1]=n[1]}this._delaunator=new Qr(e)}else delete this.collinear;const n=this.halfedges=this._delaunator.halfedges,r=this.hull=this._delaunator.hull,o=this.triangles=this._delaunator.triangles,i=this.inedges.fill(-1),s=this._hullIndex.fill(-1);for(let t=0,e=n.length;t<e;++t){const e=o[t%3==2?t-2:t+1];-1!==n[t]&&-1!==i[e]||(i[e]=t)}for(let t=0,e=r.length;t<e;++t)s[r[t]]=t;r.length<=2&&r.length>0&&(this.triangles=new Int32Array(3).fill(-1),this.halfedges=new Int32Array(3).fill(-1),this.triangles[0]=r[0],i[r[0]]=1,2===r.length&&(i[r[1]]=0,this.triangles[1]=r[1],this.triangles[2]=r[1]))}voronoi(t){return new lo(this,t)}*neighbors(t){const{inedges:e,hull:n,_hullIndex:r,halfedges:o,triangles:i,collinear:s}=this;if(s){const e=s.indexOf(t);return e>0&&(yield s[e-1]),void(e<s.length-1&&(yield s[e+1]))}const a=e[t];if(-1===a)return;let l=a,c=-1;do{if(yield c=i[l],l=l%3==2?l-2:l+1,i[l]!==t)return;if(l=o[l],-1===l){const e=n[(r[t]+1)%n.length];return void(e!==c&&(yield e))}}while(l!==a)}find(t,e,n=0){if((t=+t)!=t||(e=+e)!=e)return-1;const r=n;let o;for(;(o=this._step(n,t,e))>=0&&o!==n&&o!==r;)n=o;return o}_step(t,e,n){const{inedges:r,hull:o,_hullIndex:i,halfedges:s,triangles:a,points:l}=this;if(-1===r[t]||!l.length)return(t+1)%(l.length>>1);let c=t,u=uo(e-l[2*t],2)+uo(n-l[2*t+1],2);const f=r[t];let d=f;do{let r=a[d];const f=uo(e-l[2*r],2)+uo(n-l[2*r+1],2);if(f<u&&(u=f,c=r),d=d%3==2?d-2:d+1,a[d]!==t)break;if(d=s[d],-1===d){if(d=o[(i[t]+1)%o.length],d!==r&&uo(e-l[2*d],2)+uo(n-l[2*d+1],2)<u)return d;break}}while(d!==f);return c}render(t){const e=null==t?t=new so:void 0,{points:n,halfedges:r,triangles:o}=this;for(let e=0,i=r.length;e<i;++e){const i=r[e];if(i<e)continue;const s=2*o[e],a=2*o[i];t.moveTo(n[s],n[s+1]),t.lineTo(n[a],n[a+1])}return this.renderHull(t),e&&e.value()}renderPoints(t,e){void 0!==e||t&&"function"==typeof t.moveTo||(e=t,t=null),e=null==e?2:+e;const n=null==t?t=new so:void 0,{points:r}=this;for(let 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t.patient?t.sample?t.sampletype=t.sample:t.sample=t.sampletype=t.patient:t.sample&&(t.sampletype=t.sample);if(t.origin){switch(t.origin.toLowerCase()){case"r":case"relapse":s=r.moriginrelapse,t.isrim2=!0;break;case"g":case"germline":s=r.morigingermline,t.isrim1=!0;break;case"gp":case"germline pathogenic":s=r.morigingermlinepathogenic,t.isrim1=!0;break;case"gnp":case"germline nonpathogenic":case"germline non-pathogenic":s=r.morigingermlinenonpathogenic,t.isrim1=!0;break;case"s":case"somatic":case"diagnosis":s=r.moriginsomatic}}if(t.origin=s,!t.sample&&!t.patient)return;const a="no patient/individual name";if(t.patient?(e.patient2st[t.patient]||(e.patient2st[t.patient]={}),e.patient2st[t.patient][t.sampletype]=t.sample):(e.patient2st[a]||(e.patient2st[a]={}),e.patient2st[a][t.sampletype]=t.sample),t.sample&&t.disease)if(t.sample in e.sample2disease){if(t.disease!=e.sample2disease[t.sample])return e.snv.badlines.push([n,'conflict of disease types for sample "'+t.sample+'": '+t.disease+", 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t={dt:i?o.dtsv:o.dtfusionrna,class:i?o.mclasssv:o.mclassfusionrna,isoform:a.isoform2,mname:a.gene1||a.chr1,sample:a.sample,patient:a.patient,sampletype:a.sampletype,origin:a.origin,disease:a.disease,pairlst:[{a:{name:a.gene1,isoform:a.isoform1,strand:a.strand1,chr:a.chr1,position:a.position1},b:{name:a.gene2,isoform:a.isoform2,strand:a.strand2,chr:a.chr2,position:a.position2}}]},e=n.geneToUpper?a.gene2.toUpperCase():a.gene2;n.data[e]||(n.data[e]=[]),n.data[e].push(t)}}}else c.push([t,"missing position2",s])}function a(t){const e={};for(const n in t){if("pairlst"==n)continue;const r=t[n];"object"!=typeof r&&(e[n]=r)}if(t.pairlst){e.pairlst=[];for(const n of t.pairlst){const t={};for(const e in n)"a"!=e&&"b"!=e&&"interstitial"!=e&&(t[e]=n[e]);if(n.a){t.a={};for(const e in n.a){const r=n.a[e];"object"!=typeof r&&(t.a[e]=r)}}if(n.b){t.b={};for(const e in n.b){const r=n.b[e];"object"!=typeof r&&(t.b[e]=r)}}if(n.interstitial){t.interstitial={};for(const e in n.interstitial){const 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t>=1e9?(t/1e9).toFixed(1)+" Gb":t>=1e7?Math.ceil(t/1e6)+" Mb":t>=1e6?(t/1e6).toFixed(1)+" Mb":t>=1e4?Math.ceil(t/1e3)+" Kb":t>=1e3?(t/1e3).toFixed(1)+" Kb":t+(e?"bytes":" bp")}const ot={A:"#ca0020",T:"#f4a582",C:"#92c5de",G:"#0571b0"};function it(t){switch(t){case"A":return"T";case"T":return"A";case"C":return"G";case"G":return"C";case"a":return"t";case"t":return"a";case"c":return"g";case"g":return"c";default:return t}}function st(t){const e=[];for(let n=t.length-1;n>=0;n--)e.push(it(t[n]));return e.join("")}function at(t,e){const n={chr:t.chr,start:t.start,stop:t.stop,strand:t.strand,coding:[]};if(e.isskipexon||e.isaltexon)for(let r=0;r<t.exon.length;r++){const o=Math.max(t.codingstart,t.exon[r][0]),i=Math.min(t.codingstop,t.exon[r][1]);o>i||-1==e.skippedexon.indexOf(r)&&n.coding.push([o,i])}else if(e.a5ss||e.a3ss){const 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Et(t,e,n){if(n.query.isoform&&yt[n.query.genome].genomicNameRegexp.test(n.query.isoform))return;const[r,o]=e.makequery(n.query);if(!r)return;const i=t.newconn.prepare(r).all(o);let s;s=e.tidy?i.map((t=>e.tidy(t))):i;const a={};if(e.isgeneexpression){a.lst=s,a.isgeneexpression=!0,a.config=e.config;for(const e of t.queries)if(e.dsblocktracklst)for(const t of e.dsblocktracklst)t.type==k.tkt.junction&&(a.config.dsjunctiontk=t)}else a.lst=s;return a}function Rt(t,e){const n=[u.join(o.tpmasterdir,t.vcffile),(t.vcf.nochr?e.query.range.chr.replace("chr",""):e.query.range.chr)+":"+e.query.range.start+"-"+e.query.range.stop];return new Promise(((e,r)=>{const o=m(vt,n),i=[],s=[];o.stdout.on("data",(t=>i.push(t))),o.stderr.on("data",(t=>s.push(t))),o.on("close",(n=>{""!=s.join("").trim()&&r("error querying vcf file");const o=i.join("").trim();e({lines:""==o?[]:o.split("\n"),vcfid:t.vcf.vcfid})}))}))}function It(t){if(!t.genome)return["no genome"];const e=yt[t.genome];if(!e)return["invalid 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r=Jt(e,t,i.checkrnabam);r&&r.dnacount.ishet&&n.hetsnps.push(r)}if(n.url?n.dir=await x.cache_index(n.url,n.indexURL||n.url+".bai"):n.file&&(n.file=u.join(o.tpmasterdir,n.file)),n.hetsnps.length>0){await Dt(n,n.hetsnps,e,i.checkrnabam);for(const e of n.hetsnps)e.rnacount.nocoverage||e.rnacount.ref+e.rnacount.alt<i.checkrnabam.rna_mintotalreads||l.push(t+"."+e.pos+"."+e.ref+"."+e.alt+"\t\t\t\t\t\t\t\t"+e.rnacount.ref+"\t"+e.rnacount.alt)}}l.length>0&&await async function(t,e){const n=await function(t){const e=u.join(o.cachedir,Math.random().toString());return new Promise(((n,r)=>{c.writeFile(e,t.join("\n")+"\n",(t=>{t&&r("cannot write"),n(e)}))}))}(t),r=await Gt(n);await function(t,e){return new Promise(((n,r)=>{c.readFile(t,"utf8",((t,o)=>{if(t&&r("cannot read binom pvalue"),o){for(const t of o.trim().split("\n")){const n=t.split("\t"),r=n[0].split("."),o=e[r[0]];if(!o)continue;const i=o.hetsnps.find((t=>t.pos+"."+t.ref+"."+t.alt==r[1]+"."+r[2]+"."+r[3]));i&&(i.rnacount.pvalue=Number.parseFloat(n[10]))}n()}else n()}))}))}(r,e),c.unlink(n,(()=>{})),c.unlink(r,(()=>{}))}(l,i.checkrnabam.samples),s.checkrnabam=[];for(const n in i.checkrnabam.samples){const r=i.checkrnabam.samples[n],o=[];for(const[n,s]of t){const t={gene:n,chr:e,start:s.start,stop:s.stop},a=r.hetsnps.filter((t=>t.pos>=s.start&&t.pos<=s.stop)),l=a.filter((t=>!t.rnacount.nocoverage));if(l.length>0){const e=l.reduce(((t,e)=>t+Math.abs(e.rnacount.f-.5)),0);let n=null,r=0;for(const t of l)null!=t.rnacount.pvalue&&(null==n?n=t.rnacount.pvalue:n*=t.rnacount.pvalue,t.rnacount.pvalue<=i.checkrnabam.binompvaluecutoff&&r++);null!=n&&(t.ase={markers:a.filter((t=>t.dnacount.ishet)).length,ase_markers:r,mean_delta:e/l.length,geometricmean:Math.pow(n,1/l.length)})}let c;c=r.pairedend?await Lt(r,e,s):await 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e)r.rnacount={nocoverage:1},o.push((t.nochr?n.replace("chr",""):n)+":"+(r.pos+1)+"-"+(r.pos+1));return new Promise(((n,i)=>{const s=m(_t,["mpileup","--no-reference","-a","INFO/AD","-d",999999,"-r",o.join(","),"-q",r.rnapileup_q,"-Q",r.rnapileup_Q,t.url||t.file],{cwd:t.dir});_.createInterface({input:s.stdout}).on("line",(t=>{if("#"==t[0])return;const n=Ut(t);if(!n)return;const r=e.find((t=>t.pos==n.pos));if(r){const t=n.allele2count[r.ref]||0,e=n.allele2count[r.alt]||0;t+e>0&&(r.rnacount={ref:t,alt:e,f:e/(t+e)})}})),s.on("close",(()=>{n()}))}))}function Bt(t,e,n,r,o,i){e.hideLOHwithCNVoverlap&&zt(o);const s=[];if(i){const t=new Map;for(const[e,n]of o){const r=i.sample2group.get(e);t.has(r)||t.set(r,[]),t.get(r).push({samplename:e,items:n})}if(r)for(const e of r)if(e.dt!=k.dtsnvindel)console.log("unknown dt when grouping samples from vcf: "+e.dt);else for(const n of e.sampledata){const e=i.sample2group.get(n.sampleobj.name);t.has(e)||t.set(e,[]),t.get(e).find((t=>t.samplename==n.sampleobj.name))||t.get(e).push({samplename:n.sampleobj.name,items:[]})}for(const[e,n]of t)s.push({name:e,samples:n})}else if(t.cohort&&t.cohort.annotation&&e.groupsamplebyattr){const n=new Map,i=[];for(const[r,s]of o)Zt(r,s,n,i,t,e);if(r)for(const o of r)if(o.dt!=k.dtsnvindel)console.log("unknown dt when grouping samples from vcf data: "+o.dt);else for(const r of o.sampledata)Zt(r.sampleobj.name,[],n,i,t,e);for(const t of n.values())if(s.push(t),e.groupsamplebyattr.key2group){const n=e.groupsamplebyattr.key2group.get(t.name);n&&(t.sampletotalnum=n.samples.length)}i.length&&s.push({name:"Unannotated",samples:i});for(const e of s)for(const n of e.samples)t.cohort.annotation[n.samplename]&&(n.sampletype=t.cohort.annotation[n.samplename].sample_type)}else{const t=[];for(const[e,n]of o)t.push({samplename:e,items:n});if(r)for(const e of r)if(e.dt!=k.dtsnvindel)console.log("unknown dt when grouping 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e=s[i.groupsamplebyattr.attrlst[t].k];if(null==e)break;l.push(e)}l.unshift(a);const c=l.join(i.groupsamplebyattr.attrnamespacer);if(!n.has(c)){const t=[];for(const e of i.groupsamplebyattr.attrlst){const n=s[e.k];if(null==n)break;const r={k:e.k,kvalue:n};e.full&&(r.full=e.full,r.fullvalue=s[e.full]),t.push(r)}const e=[];for(const t of i.groupsamplebyattr.attrlst){const n=s[t.k];if(null==n)break;const r=(t.full?s[t.full]:null)||n;e.push(r)}n.set(c,{name:c,samples:[],attributes:t})}let u=!0;for(const r of n.get(c).samples)if(r.samplename==t){for(const t of e)r.items.push(t);u=!1;break}u&&n.get(c).samples.push({samplename:t,items:e})}function $t(t){return Number.isFinite(t.dna_mintotalreads)?Number.isFinite(t.rna_mintotalreads)?Number.isFinite(t.hetsnp_minbaf)?Number.isFinite(t.hetsnp_maxbaf)?Number.isFinite(t.rnapileup_q)?Number.isFinite(t.rnapileup_Q)?void 0:"invalid value for rnapileup_Q":"invalid value for rnapileup_q":"invalid value for hetsnp_maxbaf":"invalid value for 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i.dnacount.f=o+e==0?0:o/(o+e),e+o>=n.dna_mintotalreads&&i.dnacount.f>=n.hetsnp_minbaf&&i.dnacount.f<=n.hetsnp_maxbaf&&(i.dnacount.ishet=!0),i}return null}}async function Wt(t,e,n,r,i){const s=await Ht(u.join(o.tpmasterdir,e.file),n+":"+r+"-"+i),a=new Map;if(s)for(const t of s){const e=t.split("\t"),n=JSON.parse(e[3]),r=Number.parseInt(e[1]),o=Number.parseInt(e[2]);if(a.has(n.name)){const t=a.get(n.name);t.start=Math.min(t.start,r),t.stop=Math.max(t.stop,o)}else a.set(n.name,{gene:n.name,start:r,stop:o,exonunion:[]});const i=a.get(n.name);if(n.exon)for(const t of n.exon){const e=i.exonunion.find((e=>Math.max(e[0],t[0])<Math.min(e[1],t[1])));e?(e[0]=Math.min(t[0],e[0]),e[1]=Math.max(t[1],e[1])):i.exonunion.push([t[0],t[1]])}}for(const[t,e]of a)e.exonlength=e.exonunion.reduce(((t,e)=>t+e[1]-e[0]),0);return a}async function Ht(t,e,n){return new Promise(((r,o)=>{const 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Kt(t,e,n,i){if(!t.genename)return["genename missing"];const s=t.genename.toLowerCase();if(!t.chr)return["chr missing"];if(!Number.isInteger(t.start)||!Number.isInteger(t.stop))return["invalid start/stop coordinate"];if(t.stop-t.start>1e7)return["gene feature too long (> 10Mb)"];return[null,Promise.resolve().then((()=>{if(!n.file)return x.cache_index(n.url,n.indexURL)})).then((e=>new Promise(((a,l)=>{const c=[],f=m(vt,[n.file?u.join(o.tpmasterdir,n.file):n.url,t.chr+":"+t.start+"-"+t.stop],{cwd:e});_.createInterface({input:f.stdout}).on("line",(t=>{const e=t.split("\t"),n=JSON.parse(e[3]);n.gene&&n.gene.toLowerCase()==s&&n.sample&&(i&&!i.has(n.sample)||c.push(n))}));const d=[];f.stderr.on("data",(t=>d.push(t))),f.on("close",(e=>{const n=d.join("");!n||r(n)?a({id:t.id,items:c}):l(n)}))}))))]}function Xt(t,e,n,i){if(!t.chr)return["chr missing"];if(!Number.isInteger(t.start)||!Number.isInteger(t.stop))return["invalid start/stop coordinate"];if(t.stop-t.start>1e7)return["look range too big 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if(r.dt==k.dtloh){if(t.loh&&t.loh.hidden)return;if(t.loh&&t.loh.valuecutoff&&r.segmean<t.loh.valuecutoff)return;if(r.chr=n[0],r.start=Number.parseInt(n[1]),r.stop=Number.parseInt(n[2]),t.loh&&t.loh.focalsizelimit&&r.stop-r.start>=t.loh.focalsizelimit)return}else{if(r.dt!=k.dtitd)return void console.error("unknown datatype",r.dt);if(t.itd&&t.itd.hidden)return;r.chr=n[0],r.start=Number.parseInt(n[1]),r.stop=Number.parseInt(n[2])}l.push(r)}}));const f=[];c.stderr.on("data",(t=>f.push(t))),c.on("close",(e=>{const o=f.join("");if(o&&!r(o))return void a(o);const i=new Map;for(const t of l)i.has(t.sample)||i.set(t.sample,[]),i.get(t.sample).push(t);n.hideLOHwithCNVoverlap&&zt(i);const c=[];for(const[t,e]of i)for(const t of e)c.push(t);s({id:t.id,items:c})}))}))))]}function oe(t,e,n,r){if(!t.chr)return["chr missing"];if(!Number.isInteger(t.start)||!Number.isInteger(t.stop))return["invalid start/stop coordinate"];if(t.stop-t.start>1e7)return["look range too big (>10Mb)"];const o=[];for(const i of n)if(i.type==k.tkt.mdsvcf){const[n,s]=ie(t,e,i,r);if(n)return[n];o.push(s)}else{if(i.type!=k.tkt.mdssvcnv)return["unsupported track type: "+i.type];{const[e,n]=re(t,0,i,r);if(e)return[e];o.push(n)}}return[null,Promise.all(o).then((t=>{const e=[];for(const n of t)for(const t of n.items)e.push(t);return{id:t[0].id,items:e}}))]}function ie(t,e,n,i){if(!n.tracks)return"tracks[] missing from dsquery";if(!t.chr)return["chr missing"];if(!Number.isInteger(t.start)||!Number.isInteger(t.stop))return["invalid start/stop coordinate"];if(t.stop-t.start>3e6)return["look range too big (>3Mb)"];const s=[];for(const e of n.tracks){const a=Promise.resolve().then((()=>{if(!e.file)return x.cache_index(e.url,e.indexURL)})).then((s=>new Promise(((a,l)=>{const c=[],f=m(vt,[e.file?u.join(o.tpmasterdir,e.file):e.url,(e.nochr?t.chr.replace("chr",""):t.chr)+":"+t.start+"-"+(t.stop+1)],{cwd:s});_.createInterface({input:f.stdout}).on("line",(r=>{if(n.iscustom)c.push(r);else 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i={};if(t.query&&t.query.genome)i[t.query.genome]=Tt(t.query.genome);else for(const t in yt)i[t]=Tt(t);let s=!1;for(const t in yt)yt[t].blat&&(s=!0);n.send({genomes:i,debugmode:o.debugmode,headermessage:o.headermessage,base_zindex:o.base_zindex,codedate:xt.toDateString(),launchdate:kt,hasblat:s,features:e.features,dsAuth:ft.getDsAuth(t),commonOverrides:o.commonOverrides,targetPortal:o.targetPortal,cardsPath:null===(r=o.cards)||void 0===r?void 0:r.path})})),Nt.get(St+"/getDataset",(function(t,e){try{const n=yt[t.query.genome];if(!n)throw"unknown genome";if(!n.datasets)throw"genomeobj.datasets{} missing";let r;for(const e in n.datasets)if(e.toLowerCase()==t.query.dsname.toLowerCase()){r=n.datasets[e];break}if(!r)throw"invalid dsname";return r.isMds3?e.send({ds:X.client_copy(r,null,null,Nt,St)}):r.isMds?e.send({ds:jt(r)}):e.send({ds:Ct(r)})}catch(t){e.send({error:t.message||t})}})),Nt.all(St+"/genelookup",mt(yt)),Nt.all(St+"/ntseq",(async function(t,e){try{if(!t.query.coord)throw"coord 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n.refseq=e,n}))})}e.send({lst:o})}catch(t){e.send({error:t.message||t}),t.stack&&console.log(t.stack)}})),Nt.post(St+"/tkbedj",H(yt)),Nt.post(St+"/tkbedgraphdot",B(yt)),Nt.all(St+"/tkbam",z(yt)),Nt.get(St+"/gdcbam",$),Nt.get(St+"/gdc_ssms",G.handle_gdc_ssms(yt)),Nt.get(St+"/gdc_filter2topGenes",G.handle_filter2topGenes(yt)),Nt.get(St+"/tkaicheck",U(yt)),Nt.get(St+"/blat",V(yt)),Nt.all(St+"/mds3",Y(yt)),Nt.get(St+"/tkbampile",J),Nt.post(St+"/dsdata",(async function(t,e){try{if(!yt[t.query.genome])throw"invalid genome";if(!t.query.dsname)throw".dsname missing";const n=yt[t.query.genome].datasets[t.query.dsname];if(!n)throw"invalid dsname";const r=[];for(const e of n.queries)if((!t.query.expressiononly||e.isgeneexpression)&&!(t.query.noexpression&&e.isgeneexpression||e.dsblocktracklst))if(e.vcffile){const n=await Rt(e,t);r.push(n)}else{if(!e.makequery)throw"unknow type from one of ds.queries[]";{const o=Et(n,e,t);r.push(o)}}e.send({data:r})}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message||t})}})),Nt.post(St+"/tkbigwig",F),Nt.post(St+"/tkld",L(yt)),Nt.get(St+"/tabixheader",(async function(t,e){Mt(t);try{const[n,r,o]=ue(t);if(n)throw n;const i=o?await x.cache_index(r,t.query.indexURL):null,s=await x.get_header_tabix(r,i);e.send({lines:s})}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message||t})}})),Nt.all(St+"/snp",(async function(t,e){try{const n=t.query.genome;if(!n)throw"no genome";const r=yt[n];if(!r)throw"invalid genome";if(!r.snp)throw"snp is not configured for this genome";const o=[];if(t.query.byCoord){if(r.genomicNameRegexp.test(t.query.chr))throw"invalid chr name";if(!Array.isArray(t.query.ranges))throw"ranges not an array";for(const e of t.query.ranges){if(!Number.isInteger(e.start)||!Number.isInteger(e.stop)||e.start<0||e.stop<e.start)throw"invalid start/stop";if(e.stop-e.start>=100)throw"range too big";const n=await x.query_bigbed_by_coord(r.snp.bigbedfile,t.query.chr,e.start,e.stop);for(const e of n){const n=Ot(e);if(t.query.alleleLst){let e=!1;for(const r of t.query.alleleLst)if(r&&!n.alleles.includes(r)){e=!0;break}if(e)continue}o.push(n)}}}else{if(!t.query.byName)throw"unknown query method";if(!Array.isArray(t.query.lst))throw".lst[] missing";for(const e of t.query.lst){if(r.genomicNameRegexp.test(e))continue;const t=await x.query_bigbed_by_name(r.snp.bigbedfile,e);for(const e of t){const t=Ot(e);o.push(t)}}}e.send({results:o})}catch(t){return t.stack&&console.log(t.stack),e.send({error:t.message||t})}})),Nt.get(St+"/clinvarVCF",(async function(t,e){Mt(t);try{const n=yt[t.query.genome];if(!n)throw"unknown genome";if(!n.clinvarVCF)throw"no clinvar for this genome";const r=Number(t.query.pos);if(!Number.isInteger(r))throw"pos is not integer";if(r<0)throw"pos is not positive integer";if(!t.query.chr)throw"chr missing";{const e=n.chrlookup[t.query.chr.toUpperCase()];if(!e)throw"invalid chr";if(r>e.len)throw"pos out of bound"}let o;if(await x.get_lines_bigfile({args:[n.clinvarVCF.file,(n.clinvarVCF.nochr?t.query.chr.replace("chr",""):t.query.chr)+":"+r+"-"+(r+1)],callback:e=>{const[i,s,a]=q.vcfparseline(e,n.clinvarVCF);for(const e of s)e.pos==r&&e.ref==t.query.ref&&e.alt==t.query.alt&&(o=e)}}),!o)return e.send({});const i=o.info[n.clinvarVCF.infokey],s=n.clinvarVCF.categories[i];e.send({hit:{id:o.vcf_ID,value:s?s.label:i,bg:s?s.color:"#858585",textcolor:s&&s.textcolor?s.textcolor:"black"}})}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message||t})}})),Nt.post(St+"/isoformlst",(function(t,e){try{const n=yt[t.query.genome];if(!n)throw"invalid genome";if(!Array.isArray(t.query.lst))throw".lst missing";const r=[];for(const e of t.query.lst){if(n.genomicNameRegexp.test(e))continue;const t=n.genedb.getjsonbyisoform.all(e);r.push(t.map((t=>{const e=JSON.parse(t.genemodel);return t.isdefault&&(e.isdefault=!0),e})))}e.send({lst:r})}catch(t){e.send({error:t.message||t}),t.stack&&console.log(t.stack)}})),Nt.post(St+"/dbdata",(function(t,e){})),Nt.get(St+"/img",(async function(t,e){Mt(t);const[n,r,o]=ue(t);try{if(n)throw"invalid image file";const t=await c.promises.readFile(r);e.send({src:"data:image/jpeg;base64,"+new Buffer.from(t).toString("base64"),size:b(r)})}catch(n){e.send({error:n.message||n})}})),Nt.post(St+"/svmr",(function(t,e){if(t.query.file){const[n,r,o]=ue(t);if(n)return void e.send({error:"illegal file name"});c.readFile(r,"utf8",((t,n)=>{t?e.send({error:"cannot read file"}):e.send({raw:n})}))}else e.send({error:"missing file"})})),Nt.post(St+"/study",(async function(t,e){try{if(ce(t.query.file))throw"invalid file path";const n=u.join(o.tpmasterdir,t.query.file.endsWith(".json")?t.query.file:t.query.file+".json"),r=JSON.parse(await x.read_file(n));if(!r.genome)throw"genome missing";const i={};let s=0;for(const t of r.mutationset||[]){const e=N.init_bulk_flag(r.genome);if(!e)throw"init_bulk_flag() failed";if(r.mutationset.length>1&&(e.tpsetname=t.name?t.name:"set"+ ++s),i[Math.random()]=e,t.snvindel){const n=(await x.read_file(u.join(o.tpmasterdir,t.snvindel))).trim().split(/\r?\n/),r=S.parseheader(n[0],e);if(r)throw"snvindel header line error: "+r;for(let t=1;t<n.length;t++)S.parseline(t,n[t],e)}if(t.sv){const n=(await x.read_file(u.join(o.tpmasterdir,t.sv))).trim().split(/\r?\n/),r=C.parseheader(n[0],e,!0);if(r)throw"sv header line error: "+r;for(let t=1;t<n.length;t++)C.parseline(t,n[t],e,!0)}if(t.fusion){const n=(await x.read_file(u.join(o.tpmasterdir,t.fusion))).trim().split(/\r?\n/),r=C.parseheader(n[0],e,!1);if(r)throw"fusion header line error: "+r;for(let t=1;t<n.length;t++)C.parseline(t,n[t],e,!1)}if(t.svjson){const n=(await x.read_file(u.join(o.tpmasterdir,t.svjson))).trim().split(/\r?\n/),[r,i]=j.parseheader(n[0],e);if(r)throw"svjson header line error: "+r;for(let t=1;t<n.length;t++)j.parseline(t,n[t],e,i)}if(t.cnv){const n=(await x.read_file(u.join(o.tpmasterdir,t.cnv))).trim().split(/\r?\n/),r=A.parseheader(n[0],e);if(r)throw"cnv header line error: "+r;for(let t=1;t<n.length;t++)A.parseline(t,n[t],e)}if(t.itd){const n=(await x.read_file(u.join(o.tpmasterdir,t.itd))).trim().split(/\r?\n/),r=T.parseheader(n[0],e);if(r)throw"itd header line error: "+r;for(let t=1;t<n.length;t++)T.parseline(t,n[t],e)}if(t.deletion){const n=(await x.read_file(u.join(o.tpmasterdir,t.deletion))).trim().split(/\r?\n/),r=M.parseheader(n[0],e);if(r)throw"deletion header line error: "+r;for(let t=1;t<n.length;t++)M.parseline(t,n[t],e)}if(t.truncation){const n=(await x.read_file(u.join(o.tpmasterdir,t.truncation))).trim().split(/\r?\n/),r=O.parseheader(n[0],e);if(r)throw"Truncation header line error: "+r;for(let t=1;t<n.length;t++)O.parseline(t,n[t],e)}}if(r.annotations){const t=r.annotations.idkey?r.annotations.idkey:"sample";r.annotations.data={};for(const e of r.annotations.files){const n=await x.read_file(u.join(o.tpmasterdir,e));R.tsvParse(n).forEach((e=>{const n=e[t].trim();r.annotations.data[n]||(r.annotations.data[n]=[]),r.annotations.data[n].push(e)}))}}for(const t in i)ae(i[t]);delete r.mutationset,e.send({cohort:r,flagset:i})}catch(t){return void e.send({error:t.message||t})}})),Nt.post(St+"/textfile",(function(t,e){if(!t.query.file)return e.send({error:"no file"});if(ce(t.query.file))return e.send({error:"invalid file name"});const n=u.join(o.tpmasterdir,t.query.file);if(null!=t.query.from){if(!Number.isInteger(t.query.from))return void e.send({error:"invalid value for from"});if(!Number.isInteger(t.query.to))return void e.send({error:"invalid value for to"});const r=[];d(c.createReadStream(n)).on("end",(()=>{e.send({text:r.join("\n")})})).lines.map(String).skip(t.query.from-1).take(t.query.to).forEach((t=>{r.push(t)}))}else c.readFile(n,{encoding:"utf8"},((t,n)=>{t?e.send({error:"error reading 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n.send({error:r});a.checkrnabam=t.query.checkrnabam}}else{if(i=yt[t.query.genome],!i)return n.send({error:"invalid genome"});if(!i.datasets)return n.send({error:"genome is not equipped with datasets"});if(s=i.datasets[t.query.dslabel],!s)return n.send({error:"invalid dslabel"});if(t.query.getsample4disco)return function(t,e,n,r){if(t.query.iscustom)return e.send({error:"not for custom track"});if(!r.singlesamplemutationjson)return e.send({error:"singlesamplemutationjson not available for this dataset"});const i=t.query.getsample4disco,s=r.singlesamplemutationjson.samples[i];if(!s)return e.send({error:"no data"});const a=u.join(o.tpmasterdir,s);c.readFile(a,{encoding:"utf8"},((t,n)=>{if(t)return e.send({error:"error getting data for this sample"});e.send({text:n})}))}(t,n,0,s);if(t.query.gettrack4singlesample)return function(t,e,n){const r=t.query.gettrack4singlesample;if(t.query.iscustom)return e.send({error:"no server-side config available for custom 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e=n.cohort.annotation[t.name];if(!e)continue;const r=[];for(const t in n.cohort.sampleAttribute.attributes){if(n.cohort.sampleAttribute.attributes[t].clientnoshow)continue;const o=e[t];null!=o&&r.push({k:t,v:o})}r.length&&(t.attr=r)}if(n.sampleAssayTrack)for(const t of o){const e=n.sampleAssayTrack.samples.get(t.name);e&&(t.num_assay_tracks=e.length)}if(n.cohort&&n.cohort.mutation_signature)for(const t in n.cohort.mutation_signature.sets){const e=n.cohort.mutation_signature.sets[t];if(e.samples)for(const t of o)e.samples.map.has(t.name)&&(t.mutation_signature=1)}if(n.singlesamplemutationjson)for(const t of o)n.singlesamplemutationjson.samples[t.name]&&(t.disco=1);return e.send({result:o});function i(t){for(const e of t){if(o.length>10)return;-1!=e.low.indexOf(r)&&(o.find((t=>t.name==e.name))||o.push(e))}}}(t,n,s);if(t.query.assaymap)return async function(t,e,n){try{if(!n.assayAvailability)throw"assay availability not enabled for this dataset";const r=new Set(t.query.skip_termids||[]),o=new Map;for(const e in n.cohort.annotation){if(t.query.key){if(n.cohort.annotation[e][t.query.key]!=t.query.value)continue}o.set(e,new Map)}for(const[t,e]of o){const o=n.assayAvailability.samples.get(t);if(o)for(const t of n.assayAvailability.assays)r.has(t.id)||o[t.id]&&e.set(t.id,"yes")}for(const t of o.keys())0==o.get(t).size&&o.delete(t);const i={};i.totalsample=o.size,i.terms=ot({sample2term:o,terms:n.assayAvailability.assays,config:{termidorder:t.query.termidorder}}),e.send(i)}catch(t){e.send({error:t.message||t})}}(t,n,s);if(!s.queries)return n.send({error:"dataset is not equipped with queries"});if(a=s.queries[t.query.querykey],!a)return n.send({error:"invalid querykey"})}if(t.query.getexpression4gene)return async function(t,e,n,r,i){try{const n=t.query.getexpression4gene;if(!n.chr)throw"chr missing";if(!Number.isFinite(n.start))throw"invalid start pos";if(!Number.isFinite(n.stop))throw"invalid stop pos";if(!n.name)throw"unknown gene 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x.tabix_is_nochr(o,s,n)})}catch(t){t.stack&&console.error(t.stack),e.send({error:t.message||t})}})),Nt.post(St+"/translategm",(async function(t,e){try{const n=yt[t.query.genome];if(!n)throw"invalid genome";const r=t.query.gm;if(!r)throw"missing gm{}";if(!r.chr)throw"gm.chr missing";if(!r.start)throw"gm.start missing";if(!Number.isInteger(r.start))throw"gm.start not integer";if(!r.stop)throw"gm.stop missing";if(!Number.isInteger(r.stop))throw"gm.stop not integer";const o=await x.get_fasta(n,r.chr+":"+(r.start+1)+"-"+r.stop),i=k.fasta2gmframecheck(r,o);e.send({frame:i})}catch(t){e.send({error:t.message||t}),t.stack&&console.log(t.stack)}})),Nt.get(St+"/hicstat",(async function(t,e){Mt(t);try{const[n,r,o]=ue(t);if(n)throw"illegal file name";o||await x.file_is_readable(r);const i=await it(r,o);e.send({out:i})}catch(t){e.send({error:t.message||t}),t.stack&&console.log(t.stack)}})),Nt.post(St+"/hicdata",(function(t,e){const[n,r,o]=ue(t);if(n)return void e.send({error:"illegal file name"});const i=[t.query.nmeth||"NONE",r,t.query.pos1,t.query.pos2,t.query.isfrag?"FRAG":"BP",t.query.resolution],s=m(wt,i),a=_.createInterface({input:s.stdout}),l=[],c=[];let u=0,f=0;a.on("line",(e=>{const n=e.split("\t");if(3!=n.length)return void u++;const r=Number.parseInt(n[0]),o=Number.parseInt(n[1]),i=Number.parseFloat(n[2]);Number.isNaN(r)||Number.isNaN(o)||Number.isNaN(i)?f++:null!=t.query.mincutoff&&i<=t.query.mincutoff||l.push([r,o,i])})),s.stderr.on("data",(t=>c.push(t))),s.on("close",(()=>{const t=c.join("");return t?e.send({error:t}):u?e.send({error:u+" lines have other than 3 fields"}):f?e.send({error:f+" lines have non-numerical values in any of the 3 fields"}):void e.send({items:l})}))})),Nt.post(St+"/samplematrix",(function(t,e){Promise.resolve().then((()=>{const e=yt[t.query.genome];if(!e)throw"invalid genome";let n,r;if(t.query.iscustom){if(!t.query.querykey2tracks)throw"querykey2tracks{} missing for custom dataset";n={queries:{}};for(const e in t.query.querykey2tracks){const r=t.query.querykey2tracks[e];if(!r.type)throw'missing "type" for a data track';if(r.type==k.tkt.mdsvcf){const r=t.query.querykey2tracks[e];r.type=k.mdsvcftype.vcf,n.queries[e]={type:k.tkt.mdsvcf,info:r.info,tracks:[r]}}else if(r.type==k.tkt.mdssvcnv)n.queries[e]=r;else{if(r.type!=k.tkt.mdsexpressionrank)throw"unknown type of data track: "+r.type;n.queries[e]=r}}}else{if(!e.datasets)throw"genome is not equipped with datasets";if(!t.query.dslabel)throw"dslabel missing";if(n=e.datasets[t.query.dslabel],!n)throw"invalid dslabel";if(!n.queries)throw"dataset is not equipped with queries"}if(t.query.sampleset)r=new Set(t.query.sampleset);else if(t.query.limitsamplebyeitherannotation){if(!n.cohort)throw"limitsamplebyeitherannotation but no cohort in ds";if(!n.cohort.annotation)throw"limitsamplebyeitherannotation but no cohort.annotation in ds";r=new Set;for(const e in n.cohort.annotation){const o=n.cohort.annotation[e];for(const n of t.query.limitsamplebyeitherannotation)if(o[n.key]==n.value){r.add(e);break}}}const o=[];for(const e of t.query.features){let t,i=[];if(e.querykey){if(!n.queries)throw"using querykey for a feature but no ds.queries";if(t=n.queries[e.querykey],!t)throw"unknown dsquery by key "+e.querykey}else if(e.querykeylst){if(!n.queries)throw"using querykeylst for a feature but no ds.queries";for(const t of e.querykeylst){const e=n.queries[t];if(!e)throw'unknown key "'+t+'" from querykeylst';i.push(e)}if(0==i.length)throw"no valid keys in querykeylst"}else if(!e.issampleattribute)throw"unknown way to query a feature";if(e.isgenevalue){const[i,s]=Kt(e,n,t,r);if(i)throw"error with isgenevalue: "+i;o.push(s)}else if(e.iscnv){const[i,s]=Xt(e,n,t,r);if(i)throw"error with iscnv: "+i;o.push(s)}else if(e.isloh){const[i,s]=te(e,n,t,r);if(i)throw"error with isloh: "+i;o.push(s)}else if(e.isvcf){const[i,s]=ie(e,n,t,r);if(i)throw"error with isvcf: "+i;o.push(s)}else if(e.isitd){const[i,s]=ee(e,n,t,r);if(i)throw"error with isitd: "+i;o.push(s)}else if(e.issvfusion){const[i,s]=ne(e,n,t,r);if(i)throw"error with issvfusion: "+i;o.push(s)}else if(e.issvcnv){const[i,s]=re(e,n,t,r);if(i)throw"error with issvcnv: "+i;o.push(s)}else if(e.ismutation){const[t,s]=oe(e,n,i,r);if(t)throw"error with ismutation: "+t;o.push(s)}else{if(!e.issampleattribute)throw"unknown type of feature";{const[t,i]=Qt(e,n,r);if(t)throw"error with issampleattribute: "+t;o.push(i)}}}return Promise.all(o)})).then((t=>{e.send({results:t})})).catch((t=>{e.send({error:"string"==typeof t?t:t.message}),t.stack&&console.error(t.stack)}))})),Nt.get(St+"/mdssamplescatterplot",(async function(t,e){Mt(t);try{const n=yt[t.query.genome];if(!n)throw"invalid genome";const r=n.datasets[t.query.dslabel];if(!r)throw"invalid dataset";if(!r.cohort)throw"no cohort for dataset";if(!r.cohort.annotation)throw"cohort.annotation missing for dataset";const o=r.cohort.scatterplot;if(!o)throw"scatterplot not supported for this dataset";const i=[];for(const e in r.cohort.annotation){const n=r.cohort.annotation[e];if(t.query.subsetkey&&n[t.query.subsetkey]!=t.query.subsetvalue)continue;const s=n[o.x.attribute];if(!Number.isFinite(s))continue;const a=n[o.y.attribute];Number.isFinite(a)&&i.push({sample:e,x:s,y:a,s:n})}e.send({colorbyattributes:o.colorbyattributes,colorbygeneexpression:o.colorbygeneexpression,querykey:o.querykey,dots:i,tracks:o.tracks})}catch(t){t.stack&&console.error(t.stack),e.send({error:t.message||t})}})),Nt.post(St+"/mdssamplesignature",(function(t,e){try{const n=t.query;if(!n.sample)throw".sample missing";const r=yt[n.genome];if(!r)throw"invalid genome";const o=r.datasets[n.dslabel];if(!o)throw"invalid dataset";if(!o.cohort)throw"no cohort for dataset";if(!o.cohort.mutation_signature)throw"no mutation_signature for cohort";const i=[];for(const t in o.cohort.mutation_signature.sets){const e=o.cohort.mutation_signature.sets[t];if(!e.samples)continue;const r=e.samples.map.get(n.sample);if(!r)continue;const s=[];for(const t in e.signatures)r[t]&&s.push({k:t,v:r[t]});s.length&&i.push({key:t,valuename:e.samples.valuename,annotation:s.sort(((t,e)=>e.v-t.v))})}e.send({lst:i})}catch(t){t.stack&&console.error(t.stack),e.send({error:t.message||t})}})),Nt.post(St+"/mdssurvivalplot",lt(yt)),Nt.post(St+"/fimo",rt.handle_closure(yt)),Nt.all(St+"/termdb",P.handle_request_closure(yt)),Nt.all(St+"/termdb-barsql",D.handle_request_closure(yt)),Nt.post(St+"/singlecell",nt.handle_singlecell_closure(yt)),Nt.post(St+"/massSession",et.save),Nt.get(St+"/massSession",et.get),Nt.get(St+"/isoformbycoord",(async function(t,e){try{const n=yt[t.query.genome];if(!n)throw"invalid genome";if(!t.query.chr)throw"chr missing";const r=Number(t.query.pos);if(!Number.isInteger(r))throw"pos must be positive integer";const i=n.tracks.find((t=>t.__isgene));i||reject("no gene track");const s=[];await x.get_lines_bigfile({args:[u.join(o.tpmasterdir,i.file),t.query.chr+":"+r+"-"+r],callback:t=>{const e=t.split("\t")[3];if(!e)return;const r=JSON.parse(e);if(!r.isoform)return;const o={isoform:r.isoform},i=n.genedb.getjsonbyisoform.get(r.isoform);i&&(o.name=JSON.parse(i.genemodel).name,o.isdefault=i.isdefault),s.push(o)}}),e.send({lst:s})}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message||t})}})),Nt.post(St+"/ase",(async function(t,e){const n=t.query,r=3e6,i=5e5;try{const t=yt[n.genome];if(!t)throw"invalid genome";if(!n.samplename)throw"samplename missing";if(!n.chr)throw"no chr";if(!n.start||!n.stop)throw"no start/stop";if(!n.rnabarheight)throw"no rnabarheight";if(!n.dnabarheight)throw"no dnabarheight";if(!Number.isInteger(n.barypad))throw"invalid barypad";if(n.rnamax&&!Number.isFinite(n.rnamax))throw"invalid value for rnamax";if(!n.checkrnabam)throw".checkrnabam{} missing";const s=$t(n.checkrnabam);if(s)throw s;if(n.refcolor||(n.refcolor="blue"),n.altcolor||(n.altcolor="red"),!t.tracks)throw"genome.tracks[] missing";const a=t.tracks.find((t=>t.__isgene));if(!a)throw"no gene track from this genome";await async function(t,e){if(t.rnabamfile)t.rnabamfile=u.join(o.tpmasterdir,t.rnabamfile);else{if(!t.rnabamurl)throw"no file or url for rna bam";t.rnabamurl_dir=await x.cache_index(t.rnabamurl,t.rnabamindexURL||t.rnabamurl+".bai")}if(t.rnabam_nochr=await x.bam_ifnochr(t.rnabamfile||t.rnabamurl,e,t.rnabamurl_dir),t.vcffile)t.vcffile=u.join(o.tpmasterdir,t.vcffile);else{if(!t.vcfurl)throw"no file or url for vcf";t.vcfurl_dir=await x.cache_index(t.vcfurl,t.vcfindexURL)}t.vcf_nochr=await x.tabix_is_nochr(t.vcffile||t.vcfurl,t.vcfurl_dir,e)}(n,t);const l=await Wt(t,a,n.chr,n.start,n.stop),f={};if(n.stop-n.start<r)for(const[t,e]of l){const t={file:n.rnabamfile,url:n.rnabamurl,dir:n.rnabamurl_dir,nochr:n.rnabam_nochr};let r;r=n.rnabamispairedend?await Lt(t,n.chr,e):await Ft(t,n.chr,e),e.fpkm=1e9*r/(n.rnabamtotalreads*e.exonlength)}else f.fpkmrangelimit=r;const[d,h,p,y]=function(t,e){let n=t.start,r=t.stop;for(const[t,o]of e)n=Math.min(n,o.start),r=Math.max(r,o.stop);const o=t.start,i=t.stop;return[n,r,o,i]}(n,l),v=await async function(t,e,n,r,o){const i=await Vt(t.vcffile||t.vcfurl,t.vcfurl_dir),[s,a,l,c]=q.vcfparsemeta(i);if(c)throw c;const u={info:s,format:a,samples:l},f=await Ht(t.vcffile||t.vcfurl,(t.vcf_nochr?t.chr.replace("chr",""):t.chr)+":"+r+"-"+o,t.vcfurl_dir),d=[];for(const e of f||[]){const[n,r,o]=q.vcfparseline(e,u);for(const e of r){if(!k.basecolor[e.ref]||!k.basecolor[e.alt])continue;if(!e.sampledata)continue;const n=Jt(e,t.samplename,t.checkrnabam);n&&d.push(n)}}const h=[];for(const t of d)for(const[e,r]of n)if(t.pos>=r.start&&t.pos<=r.stop){h.push(t);break}return h}(n,0,l,d,h);for(const t of v)t.rnacount={nocoverage:1};let b,w;y-p>=i?f.covplotrangelimit=i:(n.rnamax?b=n.rnamax:(b=await async function(t,e,n){let r=0;return await x.get_lines_bigfile({isbam:!0,args:["depth","-r",(t.rnabam_nochr?t.chr.replace("chr",""):t.chr)+":"+(e+1)+"-"+(n+1),"-g","DUP",t.rnabamurl||t.rnabamfile],dir:t.rnabamurl_dir,callback:t=>{const e=t.split("\t");if(3!=e.length)return;const n=Number.parseInt(e[2]);Number.isInteger(n)&&(r=Math.max(r,n))}}),r}(n,p,y),f.rnamax=b),w=await async function(t,e,n,r,o){const i=new Map;for(const t of r)t.dnacount.ishet&&t.pos>=e&&t.pos<=n&&i.set(t.pos,t);const s=g(t.width*t.devicePixelRatio,(t.rnabarheight+t.barypad+t.dnabarheight)*t.devicePixelRatio),a=s.getContext("2d");t.devicePixelRatio>1&&a.scale(t.devicePixelRatio,t.devicePixelRatio);let l,c,u=!1;n-e<=t.width?(u=!0,l=1,c=t.width/(n-e),a.lineWidth=c):(c=1,l=(n-e)/t.width);return await x.get_lines_bigfile({isbam:!0,args:["depth","-r",(t.rnabam_nochr?t.chr.replace("chr",""):t.chr)+":"+(e+1)+"-"+(n+1),"-g","DUP",t.rnabamurl||t.rnabamfile],dir:t.rnabamurl_dir,callback:n=>{const r=n.split("\t");if(3!=r.length)return;const s=Number.parseInt(r[1])-1;if(!Number.isInteger(s))return;const f=Number.parseInt(r[2]);if(!Number.isInteger(f))return;const d=t.rnabarheight*Math.min(f,o)/o,h=u?(s-e)*c:(s-e)/l;a.strokeStyle="#ccc",a.beginPath(),a.moveTo(h+c/2,t.rnabarheight),a.lineTo(h+c/2,t.rnabarheight-d),a.stroke(),a.closePath(),f>o&&(a.strokeStyle="blue",a.beginPath(),a.moveTo(h+c/2,0),a.lineTo(h+c/2,2),a.stroke(),a.closePath());const p=i.get(s);p&&(p.rnacount.h=d)}}),{canvas:s,ctx:a,isbp:u,binpxw:c,binbpsize:l}}(n,p,y,v,b)),f.coveragesrc=await function(t,e,n,r,o,i,s,a){const l=[];for(const n of e)n.dnacount.ishet&&l.push((t.rnabam_nochr?t.chr.replace("chr",""):t.chr)+":"+(n.pos+1)+"-"+(n.pos+1));return new Promise(((n,r)=>{const c=m(_t,["mpileup","-q",t.checkrnabam.rnapileup_q,"-Q",t.checkrnabam.rnapileup_Q,"--no-reference","-a","INFO/AD","-d",999999,"-r",l.join(","),t.rnabamurl||t.rnabamfile],{cwd:t.rnabamurl_dir});_.createInterface({input:c.stdout}).on("line",(t=>{if("#"==t[0])return;const n=Ut(t);if(!n)return;let r;n.pos>=o&&n.pos<=i&&n.DP;const s=e.find((t=>t.pos==n.pos));if(s){s.__x=r;const t=n.allele2count[s.ref]||0,e=n.allele2count[s.alt]||0;t+e>0&&(delete s.rnacount.nocoverage,s.rnacount.ref=t,s.rnacount.alt=e,s.rnacount.f=e/(t+e))}})),c.on("close",(()=>{if(!s)return void n();const{canvas:r,ctx:l,binpxw:c}=s;l.lineWidth=Math.max(3,c);let u=0;for(const n of e)n.dnacount&&(n.pos<o||n.pos>i||(n.__x=t.width*(n.pos-o)/(i-o),u=Math.max(u,n.dnacount.ref+n.dnacount.alt)));for(const n of e){if(null==n.__x)continue;n.rnacount.nocoverage||(null==n.rnacount.h&&(n.rnacount.h=t.rnabarheight*(n.rnacount.ref+n.rnacount.alt)/a),l.strokeStyle=t.refcolor,l.beginPath(),l.moveTo(n.__x+c/2,t.rnabarheight),l.lineTo(n.__x+c/2,t.rnabarheight-(1-n.rnacount.f)*n.rnacount.h),l.stroke(),l.closePath(),l.strokeStyle=t.altcolor,l.beginPath(),l.moveTo(n.__x+c/2,t.rnabarheight-(1-n.rnacount.f)*n.rnacount.h),l.lineTo(n.__x+c/2,t.rnabarheight-n.rnacount.h),l.stroke(),l.closePath());const e=t.dnabarheight*(n.dnacount.ref+n.dnacount.alt)/u;n.dnacount.ishet&&(l.strokeStyle=t.refcolor,l.beginPath(),l.moveTo(n.__x+c/2,t.rnabarheight+t.barypad),l.lineTo(n.__x+c/2,t.rnabarheight+t.barypad+(1-n.dnacount.f)*e),l.stroke(),l.closePath(),l.strokeStyle=t.altcolor,l.beginPath(),l.moveTo(n.__x+c/2,t.rnabarheight+t.barypad+(1-n.dnacount.f)*e),l.lineTo(n.__x+c/2,t.rnabarheight+t.barypad+e),l.stroke(),l.closePath()),delete n.__x}n(r.toDataURL())}))}))}(n,v,0,0,p,y,w,b),await async function(t,e){if(0==t.length)return;const n=[];for(const r of t)r.rnacount.nocoverage||r.rnacount.ref+r.rnacount.alt<e.checkrnabam.rna_mintotalreads||n.push(r);if(0==n.length)return;const r=await function(t){const e=u.join(o.cachedir,Math.random().toString())+".snp",n=[];for(const e of t)e.rnacount.nocoverage||null!=e.rnacount.ref&&null!=e.rnacount.alt&&n.push(e.pos+"."+e.ref+"."+e.alt+"\t\t\t\t\t\t\t\t"+e.rnacount.ref+"\t"+e.rnacount.alt);return new Promise(((t,r)=>{c.writeFile(e,n.join("\n")+"\n",(n=>{n&&r("cannot write"),t(e)}))}))}(n),i=await Gt(r);await function(t,e){return new Promise(((n,r)=>{c.readFile(e,"utf8",((e,o)=>{e&&r("cannot read binom pvalue"),o||n();for(const e of o.trim().split("\n")){const n=e.split("\t"),r=t.find((t=>n[0]==t.pos+"."+t.ref+"."+t.alt));r&&(r.rnacount.pvalue=Number.parseFloat(n[10]))}n()}))}))}(t,i),c.unlink(r,(()=>{})),c.unlink(i,(()=>{}))}(v,n),f.genes=function(t,e,n){const r=[];for(const[o,i]of e){r.push(i);const e=t.filter((t=>t.pos>=i.start&&t.pos<=i.stop));if(0==e.length){i.nosnp=1;continue}i.snps=e;const o=e.filter((t=>null!=t.rnacount.pvalue));if(0==o.length){i.nornasnp=1;continue}const s=o.reduce(((t,e)=>t+Math.abs(e.rnacount.f-.5)),0);let a=null,l=0;for(const t of o)null==a?a=t.rnacount.pvalue:a*=t.rnacount.pvalue,t.rnacount.pvalue<=n.checkrnabam.binompvaluecutoff&&l++;i.ase={markers:e.filter((t=>t.dnacount.ishet)).length,ase_markers:l,mean_delta:s/o.length,geometricmean:Math.pow(a,1/o.length)}}return r}(v,l,n);let N=0;for(const t of v)t.dnacount&&t.pos>=p&&t.pos<=y&&(N=Math.max(N,t.dnacount.ref+t.dnacount.alt));f.dnamax=N,e.send(f)}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message||t})}})),Nt.post(St+"/bamnochr",(async function(t,e){const n=t.query;try{const t=yt[n.genome];if(!t)throw"invalid genome";if(n.file)n.file=u.join(o.tpmasterdir,n.file);else{if(!n.url)throw"no bam file or url";n.url_dir=await x.cache_index(n.url,n.indexURL||n.url+".bai")}const r=await x.bam_ifnochr(n.file||n.url,t,n.url_dir);e.send({nochr:r})}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message||t})}})),Nt.get(St+"/gene2canonicalisoform",(function(t,e){Mt(t);try{if(!t.query.gene)throw".gene missing";const n=yt[t.query.genome];if(!n)throw"unknown genome";if(!n.genedb.get_gene2canonicalisoform)throw"gene2canonicalisoform not supported on this genome";const r=n.genedb.get_gene2canonicalisoform.get(t.query.gene);e.send(r)}catch(t){e.send({error:t.message||t}),t.stack&&console.log(t.stack)}})),Nt.get(St+"/ideogram",(function(t,e){try{const n=yt[t.query.genome];if(!n)throw"invalid genome";if(!n.genedb.hasIdeogram)throw"ideogram not supported on this genome";if(!t.query.chr)throw".chr missing";const r=n.genedb.getIdeogramByChr.all(t.query.chr);if(!r.length)throw"no ideogram data for this chr";e.send(r)}catch(t){e.send({error:t.message||t})}})),async function(){try{await c.promises.stat(o.tpmasterdir)}catch(t){const e="Error with "+o.tpmasterdir+": "+t.code;if("validate"==process.argv[2])throw e;return void console.log("\n!!! "+e+"\n")}if(function(){if(o.features.skip_checkDependenciesAndVersions)return void console.log("SKIPPED checkDependenciesAndVersions()");const t=["jsonlite","cmprsk","hwde","lmtest"];for(const e of t){const t=p.spawnSync(o.Rscript,["-e",`suppressPackageStartupMessages(library("${e}"))`],{encoding:"utf8"});if(t.stderr.trim())throw t.stderr}{const t=p.execSync(o.samtools+" --version",{encoding:"utf8"}).trim().split("\n"),[e,n]=t[0].split(" ");if("samtools"!=e||!n)throw'cannot run "samtools version"';const[r,i]=n.split(".");if("1"!=r)throw"samtools not 1.*";if(Number(i)<10)throw"samtools not >= 1.10"}{const t=p.execSync(o.bcftools+" -v",{encoding:"utf8"}).trim().split("\n"),[e,n]=t[0].split(" ");if("bcftools"!=e||!n)throw'cannot run "bcftools version"';const[r,i]=n.split(".");if("1"!=r)throw"bcftools not 1.*";if(Number(i)<10)throw"bcftools not >= 1.10"}}(),xt=function(){const t=c.statSync(o.binpath+"/server.js").mtime,e=c.existsSync("public/bin/proteinpaint.js")&&c.statSync("public/bin/proteinpaint.js").mtime||0;return t>e?t:e}(),kt=Date(Date.now()).toString().split(" ").slice(0,5).join(" "),null!=o.base_zindex){const t=Number.parseInt(o.base_zindex);if(Number.isNaN(t)||t<=0)throw"base_zindex must be positive integer";o.base_zindex=t}if(o.jwt){if(!o.jwt.secret)throw"jwt.secret missing";if(!o.jwt.permissioncheck)throw"jwt.permissioncheck missing"}if(!o.tpmasterdir)throw".tpmasterdir missing";if(!o.cachedir)throw".cachedir missing";o.cachedir_massSession=await pe("massSession"),o.cachedir_massSessionTrash=await pe("massSessionTrash"),o.cache_snpgt={dir:await pe("snpgt"),fileNameRegexp:/[^\w]/,sampleColumn:6},o.cachedir_bam=await pe("bam"),o.cachedir_genome=await pe("genome"),o.cachedir_ssid=await pe("ssid"),o.commonOverrides&&k.applyOverrides(o.commonOverrides);if(!o.genomes)throw".genomes[] missing";if(!Array.isArray(o.genomes))throw".genomes[] not array";for(const t of o.genomes){if(!t.name)throw".name missing from a genome: "+JSON.stringify(t);if(!t.file)throw".file missing from genome "+t.name;const e=u.join(process.cwd(),t.file),n=require(c.existsSync(e)?e:t.file),r=n.default||n;if(yt[t.name]=r,!r.genomefile)throw".genomefile missing from .js file of genome "+t.name;if("NA"==r.genomefile||(r.genomefile=u.join(o.tpmasterdir,r.genomefile)),r.genomicNameRegexp||(r.genomicNameRegexp=/[^a-zA-Z0-9.:_-]/),r.tracks||(r.tracks=[]),t.tracks)for(const e of t.tracks)r.tracks.push(e);if(t.datasets&&(r.rawdslst=t.datasets),t.snp&&(r.snp=t.snp),t.blat){if(!t.blat.host)throw".blat.host missing for "+t.name;if(!t.blat.port)throw".blat.port missing for "+t.name;r.blat=t.blat}if(t.nosnp&&delete r.snp,t.nohicenzyme&&delete r.hicenzymefragment,t.nohicdomain&&delete r.hicdomain,r.genedb&&t.no_gene2canonicalisoform&&delete r.genedb.gene2canonicalisoform,t.updateAttr)for(const e of t.updateAttr){let t=r;for(const[n,r]of e.entries())if(t)if("object"==typeof r)for(const e in r)t[e]=r[e];else{if("string"==typeof t[r]){e[n+1]&&(t[r]=e[n+1]);break}t=t[r]}}}o.defaultgenome&&yt[o.defaultgenome]&&(yt[o.defaultgenome].isdefault=!0);for(const t in yt){const n=yt[t];if(!n.majorchr)throw t+": majorchr missing";if(!n.defaultcoord)throw t+": defaultcoord missing";if(await x.get_fasta(n,n.defaultcoord.chr+":"+n.defaultcoord.start+"-"+(n.defaultcoord.start+1)),n.tracks||(n.tracks=[]),"string"==typeof n.majorchr){const e=n.majorchr.trim().split(/[\s\t\n]+/),r={},o=[];for(let n=0;n<e.length;n+=2){const i=e[n],s=Number.parseInt(e[n+1]);if(Number.isNaN(s))throw t+" majorchr invalid chr size for "+i+" ("+e[n+1]+")";r[i]=s,o.push(i)}n.majorchr=r,n.majorchrorder=o}n.chrlookup={};for(const t in n.majorchr)n.chrlookup[t.toUpperCase()]={name:t,len:n.majorchr[t],major:!0};if(n.minorchr){if("string"==typeof n.minorchr){const e=n.minorchr.trim().split(/[\s\t\n]+/),r={};for(let n=0;n<e.length;n+=2){const o=Number.parseInt(e[n+1]);if(Number.isNaN(o))throw t+" minorchr invalid chr size for "+e[n]+" ("+e[n+1]+")";r[e[n]]=o}n.minorchr=r}for(const t in n.minorchr)n.chrlookup[t.toUpperCase()]={name:t,len:n.minorchr[t]}}if(n.genedb){if(!n.genedb.dbfile)throw t+": .genedb.dbfile missing";try{console.log("Connecting",n.genedb.dbfile),n.genedb.db=x.connect_db(n.genedb.dbfile)}catch(t){throw`Cannot connect genedb: ${n.genedb.dbfile}: ${t}`}n.genedb.getnamebynameorisoform=n.genedb.db.prepare("select name from genes where name=? or isoform=?"),n.genedb.getnamebyisoform=n.genedb.db.prepare("select distinct name from genes where isoform=?"),n.genedb.getjsonbyname=n.genedb.db.prepare("select isdefault,genemodel from genes where name=?"),n.genedb.getjsonbyisoform=n.genedb.db.prepare("select isdefault,genemodel from genes where isoform=?"),n.genedb.getnameslike=n.genedb.db.prepare("select distinct name from genes where name like ? limit 20");const e=ht(n.genedb.db);e.has("genealias")&&(n.genedb.getNameByAlias=n.genedb.db.prepare("select name from genealias where alias=?"),n.genedb.tableSize=n.genedb.db.prepare("select count(*) from genealias where alias=?")),e.has("gene2coord")&&(n.genedb.getCoordByGene=n.genedb.db.prepare("select * from gene2coord where name=?")),e.has("ideogram")?(n.genedb.hasIdeogram=!0,n.genedb.getIdeogramByChr=n.genedb.db.prepare("select * from ideogram where chromosome=?")):n.genedb.hasIdeogram=!1,e.has("gene2canonicalisoform")&&(n.genedb.get_gene2canonicalisoform=n.genedb.db.prepare("select isoform from gene2canonicalisoform where gene=?")),e.has("buildDate")&&(n.genedb.get_buildDate=n.genedb.db.prepare("select date from buildDate")),n.genedb.hasTable_refseq2ensembl=e.has("refseq2ensembl"),n.genedb.sqlTables=[...e],n.genedb.tableSize={};for(const t of e)"buildDate"!=t&&(n.genedb.tableSize[t]=n.genedb.db.prepare(`select count(*) as size from ${t}`).get().size)}if(n.termdbs)for(const r in n.termdbs)dt(n.termdbs[r],e.features),console.log(`${r} initiated as ${t}-level termdb`);for(const t of n.tracks)if(t.__isgene){if(!t.file)throw"Tabix file missing for gene track: "+JSON.stringify(t);try{await x.validate_tabixfile(u.join(o.tpmasterdir,t.file))}catch(e){throw"Error with "+t.file+": "+e}}if(n.proteindomain){if(!n.proteindomain.dbfile)throw t+".proteindomain: missing dbfile for sqlite db";if(!n.proteindomain.statement)throw t+".proteindomain: missing statement for sqlite db";let e;try{console.log("Connecting",n.proteindomain.dbfile),e=x.connect_db(n.proteindomain.dbfile)}catch(t){throw"Error with "+n.proteindomain.dbfile+": "+t}n.proteindomain.getbyisoform=e.prepare(n.proteindomain.statement)}if(n.snp){if(!n.snp.bigbedfile)throw t+".snp: missing bigBed file";n.snp.bigbedfile=u.join(o.tpmasterdir,n.snp.bigbedfile),await x.file_is_readable(n.snp.bigbedfile)}if(n.clinvarVCF){if(!n.clinvarVCF.file)throw t+".clinvarVCF: VCF file missing";n.clinvarVCF.file=u.join(o.tpmasterdir,n.clinvarVCF.file);try{await x.validate_tabixfile(n.clinvarVCF.file)}catch(t){throw"Error with "+n.clinvarVCF.file+": "+t}if(!n.clinvarVCF.infokey)throw t+".clinvarVCF.infokey missing";if(!n.clinvarVCF.categories)throw t+".clinvarVCF.categories{} missing";{const e=p.execSync(vt+" -H "+n.clinvarVCF.file,{encoding:"utf8"}).trim();if(!e)throw t+".clinvarVCF: no meta/header lines";const[r,o,i,s]=q.vcfparsemeta(e.split("\n"));if(s)throw t+".clinvarVCF: error parsing vcf meta: "+s.join("\n");if(!r[n.clinvarVCF.infokey])throw t+".clinvarVCF: unknown INFO key for "+n.clinvarVCF.infokey;n.clinvarVCF.info=r,n.clinvarVCF.format=o}{const e=p.execSync(vt+" -l "+n.clinvarVCF.file,{encoding:"utf8"}).trim();if(""==e)throw t+".clinvarVCF: no chr listing";n.clinvarVCF.nochr=k.contigNameNoChr(n,e.split("\n"))}}if(n.fimo_motif){if(!n.fimo_motif.db)throw t+".fimo_motif: db file missing";if(n.fimo_motif.db=u.join(o.tpmasterdir,n.fimo_motif.db),n.fimo_motif.annotationfile){const[t,e]=fe(c.readFileSync(u.join(o.tpmasterdir,n.fimo_motif.annotationfile),{encoding:"utf8"}).trim());n.fimo_motif.tf2attr={};for(const t of e)n.fimo_motif.tf2attr[t.Model.split("_")[0]]=t}}if(n.hicenzymefragment){if(!Array.isArray(n.hicenzymefragment))throw"hicenzymefragment should be an array";for(const t of n.hicenzymefragment){if(!t.enzyme)throw".enzyme missing for one element of hicenzymefragment[]";if(!t.file)throw".file missing for one element of hicenzymefragment[]";try{await x.validate_tabixfile(u.join(o.tpmasterdir,t.file))}catch(e){throw"Error with "+t.file+": "+e}}}if(n.hicdomain){if(!n.hicdomain.groups)throw".groups{} missing from hicdomain";for(const t in n.hicdomain.groups){const e=n.hicdomain.groups[t];if(!e.name)throw".name missing from hicdomain "+t;if(!e.sets)throw".set{} missing from hicdomain "+t;for(const n in e.sets){const r=e.sets[n];if(!r.name)throw".name missing from hicdomain "+t+" > "+n;if(!r.file)throw".file missing from hicdomain "+t+" > "+n;r.file=u.join(o.tpmasterdir,r.file);try{await x.validate_tabixfile(r.file)}catch(t){throw"Error with "+r.file+": "+t}}}}if(n.rawdslst){n.datasets={};for(const e of n.rawdslst){if(!e.name)throw"a nameless dataset from "+t;if(n.datasets[e.name])throw t+" has duplicating dataset name: "+e.name;if(!e.jsfile)throw"jsfile not available for dataset "+e.name+" of "+t;const r=u.join(process.cwd(),e.jsfile),o=require(c.existsSync(r)?r:e.jsfile),i="function"==typeof o?o(k):"function"==typeof(null==o?void 0:o.default)?o.default(k):o.default||o;if(Q(i,e),i.noHandleOnClient=e.noHandleOnClient,i.label=e.name,i.genomename=t,n.datasets[i.label]=i,i.isMds3)try{await X.init(i,n,e,Nt,St)}catch(t){throw t.stack&&console.log(t.stack),"Error with mds3 dataset "+i.label+": "+t}else if(i.isMds)try{await ge(i,n,e)}catch(t){throw"Error with mds dataset "+i.label+": "+t}else he(i,n)}de(),delete n.rawdslst}}}().then((async()=>{if(console.log(`\n${new Date} ${o.commitHash||""}`),console.log("\nValidation succeeded.\n"),"validate"!=process.argv[2])if("phewas-precompute"!=process.argv[2])await async function(){try{if(o.preListenScript){const{cmd:t,args:e}=o.preListenScript,n=p.spawnSync(t,e,{encoding:"utf-8"});if(n.stderr.trim())throw n.stderr.trim();console.log(n.stdout)}o.appEnable&&o.appEnable.forEach((t=>Nt.enable(t)));const t=o.port,e=`STANDBY AT PORT ${t}`;if(o.ssl){const n={key:c.readFileSync(o.ssl.key),cert:c.readFileSync(o.ssl.cert)},r=await l.createServer(n,Nt);return r.listen(t,"0.0.0.0",(()=>{console.log(`HTTPS ${e}`)})),r}{const n=await a.createServer(Nt);return n.listen(t,"0.0.0.0",(()=>{process.send&&process.send("ready"),console.log(e)})),n}}catch(t){throw t}}();else{const t=process.argv[3],e=process.argv[4],n=yt[t];if(!n)throw"invalid genome name: "+t;const r=n.datasets[e];if(!r)throw"invalid dataset: "+e;at.do_precompute(r)}else console.log("You may now run the server.")})).catch((t=>{let e=1;if(!c.existsSync(o.tpmasterdir)){const t=o.maintenance||{};if("start"in t&&"stop"in t&&"tpErrorCode"in t){const n=+new Date(t.start),r=+new Date(t.stop),o=+new Date;n<=o&&o<=r&&(e=t.tpErrorCode)}}t.stack&&console.log(t.stack),e?console.error("\n!!!\n"+t+"\n\n"):console.log("\n!!!\n"+t+"\n\n"),process.exit(e)})),e.log=Mt,e.boxplot_getvalue=function(t){const e=t.length;if(e<5)return{out:t};const n=t[Math.floor(e/2)].value,r=t[Math.floor(e/4)].value,o=t[Math.floor(3*e/4)].value,i=t[Math.floor(.05*e)].value,s=t[Math.floor(.95*e)].value,a=(t[Math.floor(.01*e)].value,o-r);let l,c;if(0==a)l=0,c=0;else{const n=t.findIndex((t=>t.value>r-1.5*a));l=t[-1==n?0:n].value;const i=t.findIndex((t=>t.value>o+1.5*a));c=t[-1==i?e-1:i-1].value}const u=t.filter((t=>t.value<r-1.5*a||t.value>o+1.5*a));return{w1:l,w2:c,p05:i,p25:r,p50:n,p75:o,p95:s,iqr:a,out:u}};function ae(t){delete t.mclasslabel2key,delete t.sample2disease,delete t.patient2ori2sample}const le=Object.freeze([".bam",".bai",".gz",".tbi",".csi",".bw",".bb"]);function ce(t,e=!1,n=!0){if("/"==t[0])return!0;if(t.includes('"')||t.includes("'"))return!0;if(t.includes("|")||t.includes("&"))return!0;if(t.includes(" "))return!0;if(-1!=t.indexOf(".."))return!0;if(t.match(/(\<script|script\>)/i))return!0;if(e&&o.whiteListPaths){let e=!0;for(const n of o.whiteListPaths){if(t.startsWith(n)||"!"!=n[0]&&gt(t,n)){e=!1;break}if("!"==n[0]&&!gt(t,n)){e=!0;break}}if(e)return!0}if(n)for(const e of le)if(e===u.extname(t).toLowerCase())return!0;return!1}function ue(t,e=!0){let n=null,r=!1;if(t.query.file){if(n=t.query.file,ce(n,e,!1))return["illegal file path"];n=u.join(o.tpmasterdir,n)}else if(t.query.url){if(n=t.query.url,n.includes(" "))return["url must not contain whitespace"];if(n.includes('"')||n.includes("'"))return["url must not contain single or double quotes"];r=!0}return n?[null,n,r]:["file unspecified"]}function fe(t){const e=t.split(/\r?\n/);if(e.length<=1||!e[0])return[null,[]];const n=e[0].split("\t"),r=[];for(let t=1;t<e.length;t++){if("#"==e[t][0])continue;const o=e[t].split("\t"),i={};for(let t=0;t<n.length;t++){const e=o[t];e&&(i[n[t]]=e)}r.push(i)}return[null,r]}async function de(){const t=await c.promises.readdir(o.cachedir_massSession);try{t.forEach((async t=>{const e=(await c.promises.stat(u.join(o.cachedir_massSession,t))).birthtime,n=new Date,r=new Date(e),i=o.features.massSessionDuration||30;Math.round((n.getTime()-r.getTime())/864e5)>i&&(await c.promises.copyFile(u.join(o.cachedir_massSession,t),u.join(o.cachedir_massSessionTrash,t)),await c.promises.unlink(u.join(o.cachedir_massSession,t)),console.log("File deleted: ",t,e))}))}catch(t){throw`Error: ${t}`}}function he(t,e){if(t.dbfile)try{console.log("Connecting",t.dbfile),t.newconn=x.connect_db(t.dbfile)}catch(e){throw"Error with "+t.dbfile+": "+e}if(t.snvindel_attributes)for(const e of t.snvindel_attributes)if(e.lst)for(const t of e.lst)t.get=t.get.toString();else e.get=e.get.toString();if(t.cohort){if(t.cohort.levels){if(!Array.isArray(t.cohort.levels))throw"cohort.levels must be array for "+t.genomename+"."+t.label;if(0==t.cohort.levels.length)throw"levels is blank array for cohort of "+t.genomename+"."+t.label;for(const e of t.cohort.levels)if(!e.k)throw".k key missing in one of the levels, .cohort, in "+t.genomename+"."+t.label}if(t.cohort.fromdb){if(!t.cohort.fromdb.sql)throw".sql missing from ds.cohort.fromdb in "+t.genomename+"."+t.label;const e=t.newconn.prepare(t.cohort.fromdb.sql).all();delete t.cohort.fromdb,t.cohort.raw=e,console.log(e.length+" rows retrieved for "+t.label+" sample annotation")}if(t.cohort.files){let e=[];for(const n of t.cohort.files){if(!n.file)throw".file missing from one of cohort.files[] for "+t.genomename+"."+t.label;const r=c.readFileSync(u.join(o.tpmasterdir,n.file),"utf8").trim();if(!r)throw n.file+" is empty for "+t.genomename+"."+t.label;e=[...e,...R.tsvParse(r)]}delete t.cohort.files,t.cohort.raw?t.cohort.raw=[...t.cohort.raw,...e]:t.cohort.raw=e,console.log(e.length+" rows retrieved for "+t.label+" sample annotation")}if(t.cohort.tosampleannotation){if(!t.cohort.tosampleannotation.samplekey)throw".samplekey missing from .cohort.tosampleannotation for "+t.genomename+"."+t.label;if(!t.cohort.key4annotation)throw".cohort.key4annotation missing when .cohort.tosampleannotation is on for "+t.genomename+"."+t.label}}if(!t.queries)throw".queries missing from dataset "+t.label+", "+t.genomename;if(!Array.isArray(t.queries))throw t.label+".queries is not array";for(const n of t.queries){const r=me(n,t,e);if(r)throw'Error parsing a query in "'+t.label+'": '+r}if(t.vcfinfofilter){const e=k.validate_vcfinfofilter(t.vcfinfofilter);if(e)throw t.label+": vcfinfofilter error: "+e}if(t.url4variant)for(const e of t.url4variant){if(!e.makelabel)throw"makelabel() missing for one item of url4variant from "+t.label;if(!e.makeurl)throw"makeurl() missing for one item of url4variant from "+t.label;e.makelabel=e.makelabel.toString(),e.makeurl=e.makeurl.toString()}}async function pe(t){const e=u.join(o.cachedir,t);try{await c.promises.stat(e)}catch(t){if("ENOENT"!=t.code)throw"error stating dir";try{await c.promises.mkdir(e)}catch(t){throw"cannot make dir"}}return e}function me(t,e,n){if(!t.name)return".name missing";if(t.dsblocktracklst){if(!Array.isArray(t.dsblocktracklst))return"dsblocktracklst not an array in "+e.label;for(const n of t.dsblocktracklst){if(!n.type)return"missing type for a blocktrack of "+e.label;if(!n.file&&!n.url)return"neither file or url given for a blocktrack of "+e.label}}else if(t.vcffile){const e=p.execSync(vt+" -H "+u.join(o.tpmasterdir,t.vcffile),{encoding:"utf8"}).trim();if(""==e)return"no meta lines in VCF file "+t.vcffile+" of query "+t.name;const[r,i,s,a]=q.vcfparsemeta(e.split("\n"));if(a)return"error parsing VCF meta lines of "+t.vcffile+": "+a.join("; ");t.vcf={vcfid:Math.random().toString(),info:r,format:i,samples:s},t.hlinfo&&(t.vcf.hlinfo=t.hlinfo,delete t.hlinfo),t.infopipejoin&&(t.vcf.infopipejoin=t.infopipejoin,delete t.infopipejoin);const l=p.execSync(vt+" -l "+u.join(o.tpmasterdir,t.vcffile),{encoding:"utf8"}).trim();if(""==l)return"tabix -l found no chromosomes/contigs in "+t.vcffile+" of query "+t.name;t.vcf.nochr=k.contigNameNoChr(n,l.split("\n"));let c=0;if(r)for(const t in r)c++;console.log("Parsed vcf meta from "+t.vcffile+": "+c+" INFO, "+s.length+" sample, "+(t.vcf.nochr?'no "chr"':'has "chr"'))}else{if(!t.makequery)return"do not know how to parse query: "+t.name;if(t.isgeneexpression){if(!t.config)return"config object missing for gene expression query of "+t.name;t.config.maf&&(t.config.maf.get=t.config.maf.get.toString())}}}async function ge(t,e,n){if((t.isMds2||t.isMds3||t.isMds)&&Q(t,n),t.assayAvailability){if(!t.assayAvailability.file)throw".assayAvailability.file missing";if(!t.assayAvailability.assays)throw".assayAvailability.assays[] missing";Object.freeze(t.assayAvailability.assays),t.assayAvailability.samples=new Map;for(const e of c.readFileSync(u.join(o.tpmasterdir,t.assayAvailability.file),{encoding:"utf8"}).trim().split("\n")){const[n,r]=e.split("\t");t.assayAvailability.samples.set(n,JSON.parse(r))}console.log(t.assayAvailability.samples.size+" samples with assay availability ("+t.label+")")}if(t.gene2mutcount){if(!t.gene2mutcount.dbfile)throw".gene2mutcount.dbfile missing";try{console.log("Connecting",t.gene2mutcount.dbfile),t.gene2mutcount.db=x.connect_db(t.gene2mutcount.dbfile),console.log("DB connected for "+t.label+": "+t.gene2mutcount.dbfile)}catch(t){throw"Error connecting db at ds.gene2mutcount.dbfile"}}if(t.sampleAssayTrack){if(!t.sampleAssayTrack.file)throw".file missing from sampleAssayTrack";t.sampleAssayTrack.samples=new Map;let e=0,n=new Set;for(const r of c.readFileSync(u.join(o.tpmasterdir,t.sampleAssayTrack.file),{encoding:"utf8"}).trim().split("\n")){if(!r)continue;if("#"==r[0])continue;const[o,i,s]=r.split("\t");if(!i||!s)continue;if(!t.sampleAssayTrack.samples.has(o)){if(t.cohort&&t.cohort.annotation&&!t.cohort.annotation[o]){n.add(o);continue}t.sampleAssayTrack.samples.set(o,[])}const a=JSON.parse(s);if(!k.tkt[a.type])throw"invalid type from a sample track: "+s;a.name||(a.name=o+" "+i),a.assayName=i,t.sampleAssayTrack.samples.get(o).push(a),e++}console.log(e+" assay-tracks from "+t.sampleAssayTrack.samples.size+" samples ("+t.label+")"),n.size&&console.log("Error: "+n.size+" samples with assay tracks are unannotated: "+[...n].join(" "))}if(t.singlesamplemutationjson){const e=t.singlesamplemutationjson;if(!e.file)throw".file missing from singlesamplemutationjson";e.samples={};let n=0;for(const t of c.readFileSync(u.join(o.tpmasterdir,e.file),{encoding:"utf8"}).trim().split("\n")){if(!t)continue;if("#"==t[0])continue;const[r,o]=t.split("\t");r&&o&&(n++,e.samples[r]=o)}console.log(n+" samples for disco plot")}if(t.cohort&&t.cohort.db&&t.cohort.termdb&&await K.init_db(t,Nt,St),t.cohort&&t.cohort.files){if(!Array.isArray(t.cohort.files))throw".cohort.files is not array";if(!t.cohort.tohash)throw".tohash() missing from cohort";if("function"!=typeof t.cohort.tohash)throw".cohort.tohash is not function";if(!t.cohort.samplenamekey)throw".samplenamekey missing";if(t.cohort.annotation={},t.cohort.mutation_signature){const e=t.cohort.mutation_signature;if(!e.sets)throw".mutation_signature.sets missing";for(const n in e.sets){const r=e.sets[n];if(r.name||(r.name=n),!r.signatures)throw".signatures{} missing from a signature set";if(r.samples){if(!r.samples.file)throw".samples.file missing from a signature set";const[e,n]=fe(c.readFileSync(u.join(o.tpmasterdir,r.samples.file),{encoding:"utf8"}).trim());r.samples.map=new Map;for(const e of n){const n=e[t.cohort.samplenamekey];if(!n)throw t.cohort.samplenamekey+" missing in file "+r.samples.file;r.samples.map.set(n,e);for(const t in r.signatures)if(e[t]){const o=Number.parseFloat(e[t]);if(Number.isNaN(o))throw"mutation signature value is not float: "+e[t]+" from sample "+n;r.samples.skipzero&&0==o?delete e[t]:e[t]=o}}}}}if(t.cohort.attributes){if(!t.cohort.attributes.lst)throw".lst[] missing for cohort.attributes";if(!Array.isArray(t.cohort.attributes.lst))return".cohort.attributes.lst is not array";for(const e of t.cohort.attributes.lst){if(!e.key)throw".key missing from one of the .cohort.attributes.lst[]";if(!e.label)throw".label missing from one of the .cohort.attributes.lst[]";if(!e.values)throw".values{} missing from "+e.label+" of .cohort.attributes.lst";for(const t in e.values)if(!e.values[t].label)throw".label missing from one value of "+e.label+" in .cohort.attributes.lst"}if(t.cohort.attributes.defaulthidden)for(const e in t.cohort.attributes.defaulthidden){const n=t.cohort.attributes.lst.find((t=>t.key==e));if(!n)throw"invalid defaulthidden key: "+e;for(const r in t.cohort.attributes.defaulthidden[e])if(!n.values[r])throw"invalid defaulthidden value "+r+" for "+e}}if(t.cohort.hierarchies){if(!t.cohort.hierarchies.lst)throw".lst[] missing from .cohort.hierarchies";if(!Array.isArray(t.cohort.hierarchies.lst))throw".cohort.hierarchies.lst is not array";for(const e of t.cohort.hierarchies.lst){if(!e.name)throw".name missing from one hierarchy";if(!e.levels)throw".levels[] missing from one hierarchy";if(!Array.isArray(e.levels))throw".levels is not array from one hierarchy";for(const t of e.levels)if(!t.k)throw".k missing from one level in hierarchy "+e.name}}if(t.cohort.sampleAttribute){if(!t.cohort.sampleAttribute.attributes)throw"attributes{} missing from cohort.sampleAttribute";for(const e in t.cohort.sampleAttribute.attributes){const n=t.cohort.sampleAttribute.attributes[e];if(!n.label)throw".label missing for key "+e+" from cohort.sampleAttribute.attributes";if(n.values)for(const t in n.values){const e=n.values[t];if("object"!=typeof e)throw'value "'+t+'" not pointing to {} from sampleAttribute';e.name||(e.name=t)}if(n.showintrack&&!n.isinteger&&!n.isfloat)throw n.label+": .showintrack requires .isinteger or .isfloat"}}if(t.cohort.scatterplot){if(!t.cohort.sampleAttribute)throw".sampleAttribute missing but required for .cohort.scatterplot";const e=t.cohort.scatterplot;if(!e.querykey)throw".querykey missing from .cohort.scatterplot";{if(!t.queries)throw".cohort.scatterplot.querykey in use but ds.queries{} missing";const n=t.queries[e.querykey];if(!n)throw"unknown query by .cohort.scatterplot.querykey: "+e.querykey;if(n.type!=k.tkt.mdssvcnv)throw"type is not "+k.tkt.mdssvcnv+" of the track pointed to by .cohort.scatterplot.querykey"}if(e.colorbygeneexpression){if(!e.colorbygeneexpression.querykey)throw"querykey missing from .cohort.scatterplot.colorbygeneexpression";if(!t.queries)throw".cohort.scatterplot.colorbygeneexpression in use but ds.queries{} missing";const n=t.queries[e.colorbygeneexpression.querykey];if(!n)throw"unknown query by .cohort.scatterplot.colorbygeneexpression.querykey: "+e.colorbygeneexpression.querykey;if(!n.isgenenumeric)throw"isgenenumeric missing from the track pointed to by .cohort.scatterplot.colorbygeneexpression.querykey"}if(e.tracks,!e.x)throw".x missing from .cohort.scatterplot";if(!e.x.attribute)throw".attribute missing from .cohort.scatterplot.x";const n=t.cohort.sampleAttribute.attributes[e.x.attribute];if(!n)throw"scatterplot.x.attribute is not defined in sampleAttribute";if(!n.isfloat)throw'scatterplot.x is not "isfloat"';if(!e.y)throw".y missing from .cohort.scatterplot";if(!e.y.attribute)throw".attribute missing from .cohort.scatterplot.y";const r=t.cohort.sampleAttribute.attributes[e.y.attribute];if(!r)throw"scatterplot.y.attribute is not defined in sampleAttribute";if(!r.isfloat)throw'scatterplot.y is not "isfloat"';if(e.colorbyattributes)for(const n of e.colorbyattributes){if(!n.key)throw".key missing from one of scatterplot.colorbyattributes";const e=t.cohort.sampleAttribute.attributes[n.key];if(!e)throw"unknown attribute by key "+n.key+" from scatterplot.colorbyattributes";n.label=e.label,n.values=e.values}}for(const e of t.cohort.files){if(!e.file)throw".file missing from one of .cohort.files";const[n,r]=fe(c.readFileSync(u.join(o.tpmasterdir,e.file),{encoding:"utf8"}).trim());if(n)throw'cohort annotation file "'+e.file+'": '+n;console.log(t.label+": "+r.length+" samples loaded from annotation file "+e.file),r.forEach((e=>{for(const n in e){let r;t.cohort.sampleAttribute&&(r=t.cohort.sampleAttribute.attributes[n]),r||t.cohort.termdb&&t.cohort.termdb.termjson&&t.cohort.termdb.termjson.map&&(r=t.cohort.termdb.termjson.map.get(n)),r&&(r.isfloat?e[n]=Number.parseFloat(e[n]):r.isinteger&&(e[n]=Number.parseInt(e[n])))}t.cohort.tohash(e,t)}))}if(t.cohort.annorows=Object.values(t.cohort.annotation),console.log(t.label+": total samples from sample table: "+t.cohort.annorows.length),t.cohort.survivalplot){const e=t.cohort.survivalplot;if(!e.plots)throw".plots{} missing from survivalplot";e.init={plottypes:[]};for(const t in e.plots){const n=e.plots[t];if(!n.name)throw".name missing from survivalplot "+t;if(!n.serialtimekey)throw".serialtimekey missing from survivalplot "+t;if(!n.iscensoredkey)throw".iscensoredkey missing from survivalplot "+t;if(!n.timelabel)throw".timelabel missing from survivalplot "+t;n.key=t,e.init.plottypes.push({key:t,name:n.name,timelabel:n.timelabel})}if(e.samplegroupattrlst){e.init.samplegroupings=[];for(const n of e.samplegroupattrlst){if(!n.key)throw".key missing from an attr of samplegroupattrlst for survival";const r=t.cohort.sampleAttribute.attributes[n.key];if(!r)throw'unknown attribute key "'+n.key+'" from survival samplegroupattrlst';const o=new Map;for(const r in t.cohort.annotation){const i=t.cohort.annotation[r],s=i[n.key];if(null==s)continue;let a=!1;for(const t in e.plots)if(null!=i[e.plots[t].serialtimekey]){a=!0;break}a&&(o.has(s)?o.set(s,o.get(s)+1):o.set(s,1))}if(0==o.size)throw'no value found for "'+n.key+'" from survival samplegroupattrlst';const i=[];for(const[t,e]of o)i.push({value:t,count:e});e.init.samplegroupings.push({key:n.key,label:r.label,values:i})}}}}if(t.mutationAttribute){if(!t.mutationAttribute.attributes)throw"attributes{} missing from mutationAttribute";for(const e in t.mutationAttribute.attributes){const n=t.mutationAttribute.attributes[e];if(!n.label)throw".label missing for key "+e+" from mutationAttribute.attributes";if(!n.appendto_link&&n.values)for(const t in n.values){if(!n.values[t].name)throw".name missing for value "+t+" of key "+e+" from mutationAttribute.attributes"}}}if(t.alleleAttribute){if(!t.alleleAttribute.attributes)throw"attributes{} missing from alleleAttribute";for(const e in t.alleleAttribute.attributes){const n=t.alleleAttribute.attributes[e];if(!n.label)throw".label missing for key "+e+" from alleleAttribute.attributes";if(!n.isnumeric){if(!n.values)throw".values{} missing for non-numeric key "+e+" from alleleAttribute.attributes";for(const t in n.values){if(!n.values[t].name)throw".name missing for value "+t+" of key "+e+" from alleleAttribute.attributes"}}}}if(t.locusAttribute){if(!t.locusAttribute.attributes)throw"attributes{} missing from locusAttribute";for(const e in t.locusAttribute.attributes){const n=t.locusAttribute.attributes[e];if(!n.label)throw".label missing for key "+e+" from locusAttribute.attributes";if(!n.isnumeric&&!n.appendto_link){if(!n.values)throw".values{} missing for non-numeric key "+e+" from locusAttribute.attributes";for(const t in n.values){if(!n.values[t].name)throw".name missing for value "+t+" of key "+e+" from locusAttribute.attributes"}}}}if(t.queries)for(const r in t.queries){if(n.remove_queries&&-1!=n.remove_queries.indexOf(r)){delete t.queries[r];continue}const o=t.queries[r];if(n.hide_queries&&-1!=n.hide_queries.indexOf(r)&&(o.hideforthemoment=1),o.istrack){if(!o.type)throw".type missing for track query "+r;if(o.viewrangeupperlimit&&!Number.isInteger(o.viewrangeupperlimit))throw".viewrangeupperlimit should be integer for track query "+r;if(o.type==k.tkt.mdsjunction){const n=ve(o,t,e);if(n)throw r+" (mdsjunction) error: "+n}else if(o.type==k.tkt.mdscnv){const n=we(o,t,e);if(n)throw r+" (mdscnv) error: "+n}else if(o.type==k.tkt.mdssvcnv){const n=xe(o,t,e);if(n)throw r+" (svcnv) error: "+n}else{if(o.type!=k.tkt.mdsvcf)throw"unknown track type for a query: "+o.type+" "+r;{const n=await qe(o,t,e);if(n)throw r+" (vcf) error: "+n}}ye(o,t)}else{if(!o.isgenenumeric)throw"unknown type of query from "+r;{const n=ke(o,t,e);if(n)throw r+" (genenumeric) error: "+n}}}if(t.track&&await K.init_track(t,e),t.annotationsampleset2matrix){if(!t.cohort)throw"ds.cohort misssing when annotationsampleset2matrix is in use";if(!t.cohort.annotation)throw"ds.cohort.annotation misssing when annotationsampleset2matrix is in use";if(!t.queries)throw"ds.queries misssing when annotationsampleset2matrix is in use";if(!t.annotationsampleset2matrix.key)throw".key STR missing in annotationsampleset2matrix";if(!t.annotationsampleset2matrix.groups)throw".groups{} missing in annotationsampleset2matrix";if("object"!=typeof t.annotationsampleset2matrix.groups)throw"ds.annotationsampleset2matrix.groups{} not an object";for(const e in t.annotationsampleset2matrix.groups){const n=t.annotationsampleset2matrix.groups[e];if(!n.groups||!Array.isArray(n.groups)||0==n.groups.length)throw".groups[] must be nonempty array in "+e;for(const r of n.groups){if(!r.name)throw".name missing from one of .groups[] in "+e;const n=r.matrixconfig;if(!n)throw".matrixconfig missing from one of .groups[] of "+e;if(!n.features)throw".features[] missing from group "+e;if(!Array.isArray(n.features))throw".features[] should be array from group "+e;if(0==n.features.length)throw".features[] zero length from group "+e;for(const r of n.features){if(t.annotationsampleset2matrix.commonfeatureattributes)for(const e in t.annotationsampleset2matrix.commonfeatureattributes)null==r[e]&&(r[e]=t.annotationsampleset2matrix.commonfeatureattributes[e]);if(!r.ismutation)return"unknown feature type from group "+e;if(!r.position)throw"position missing from feature "+JSON.stringify(r)+" from group "+e;if(!r.querykeylst)throw".querykeylst[] missing from ismutation feature from group "+e;if(!Array.isArray(r.querykeylst))throw".querykeylst[] not an array from ismutation feature from group "+e;if(0==r.querykeylst.length)throw".querykeylst[] zero length from ismutation feature from group "+e;for(const n of r.querykeylst)if(!t.queries[n])throw'unknown query key "'+n+'" from ismutation feature of group '+e}if(!n.limitsamplebyeitherannotation)throw".limitsamplebyeitherannotation[] missing from group "+e;if(!Array.isArray(n.limitsamplebyeitherannotation))throw".limitsamplebyeitherannotation[] should be array from group "+e;if(0==n.limitsamplebyeitherannotation.length)throw".limitsamplebyeitherannotation[] zero length from group "+e;for(const t of n.limitsamplebyeitherannotation){if(!t.key)throw"key missing from one of limitsamplebyeitherannotation from group "+e;if(!t.value)throw"value missing from one of limitsamplebyeitherannotation from group "+e}}}delete t.annotationsampleset2matrix.commonfeatureattributes}}function ye(t,e){if(t.groupsamplebyattr){t.groupsamplebyattr.key2group=new Map;for(const n in e.cohort.annotation)Zt(n,[],t.groupsamplebyattr.key2group,[],e,t)}}function ve(t,e,n){if(t.readcountCutoff&&(!Number.isInteger(t.readcountCutoff)||t.readcountCutoff<1))return"readcountCutoff must be positive integer";let r;if(t.file){const[e,n]=se(t.file);if(e)return"tabix file error: "+e;t.file=n,r=n}else{if(!t.url)return"no file or url given for mdsjunction "+t.name;r=t.url}const o={encoding:"utf8"};const i=p.execSync(vt+" -H "+r,o).trim();if(i){const n=i.split("\n");if(1!=n.length)return"mdsjunction file has multiple header lines (begin with #), but should have just 1";const r=n[0].split("\t");if(r[5]){t.samples=r.slice(5),t.attributeSummary=be(t.samples,e),t.hierarchySummary=_e(t.samples,e);for(const e in t.hierarchySummary){let n=0;for(const r in t.hierarchySummary[e])n++;console.log(n+" "+e+" hierarchy levels for "+t.name)}}}{const e=p.execSync(vt+" -l "+r,o).trim();if(!e)return"no chromosomes found";t.nochr=k.contigNameNoChr(n,e.split("\n"))}if(console.log("(mdsjunction) "+t.name+": "+(t.samples?t.samples.length:0)+" samples, "+(t.nochr?'no "chr"':'has "chr"')),!t.infoFilter)return".infoFilter{} missing";if(!t.infoFilter.lst)return".lst[] missing from .infoFilter";for(const e of t.infoFilter.lst){if(!e.key)return".key missing from one of infoFilter";if(!e.label)return".label missing from one of infoFilter";if(!e.categories)return".categories missing from one of infoFilter";for(const t in e.categories){if(!e.categories[t].label)return".label missing from one category of "+e.label;if(!e.categories[t].color)return".color missing from on category of "+e.label}if(e.hiddenCategories){for(const t in e.hiddenCategories)if(!e.categories[t])return"invalid hidden key "+t+" of "+e.label}else e.hiddenCategories={}}if(!t.singlejunctionsummary)return".singlejunctionsummary missing but is currently required from "+t.name;if(t.singlejunctionsummary.readcountboxplotpercohort){if(!t.singlejunctionsummary.readcountboxplotpercohort.groups)return".groups[] missing from query.singlejunctionsummary.readcountboxplotpercohort for "+t.name;for(const e of t.singlejunctionsummary.readcountboxplotpercohort.groups){if(!e.key)return".key missing from one group of query.singlejunctionsummary.readcountboxplotpercohort.groups";if(!e.label)return".label missing from one group of query.singlejunctionsummary.readcountboxplotpercohort.groups"}}}function be(t,e){if(!(e.cohort&&e.cohort.annotation&&e.cohort.attributes&&t))return;const n={};for(const r of e.cohort.attributes.lst){const o={};for(const t in r.values)o[t]=0;for(const n of t){const t=e.cohort.annotation[n];if(!t)continue;const i=t[r.key];null!=i&&(i in o&&o[i]++)}n[r.key]=o}return n}function _e(t,e){if(!e.cohort||!e.cohort.annotation||!e.cohort.hierarchies||0==t.length)return;const n=[];for(const r of t){const t=e.cohort.annotation[r];t&&n.push(t)}const r={};for(const t of e.cohort.hierarchies.lst){const e=y(n,t.levels),o=E()(e);o.sum((t=>t.value));const i={};o.eachBefore((t=>{i[t.id]=t.value})),r[t.name]=i}return r}function we(t,e,n){let r;if(t.file){const[e,n]=se(t.file);if(e)return"tabix file error: "+e;r=n}else{if(!t.url)return"no file or url given for (mdscnv) "+t.name;r=t.url}const o={encoding:"utf8"};const i=p.execSync(vt+" -H "+r,o).trim();if(i){const n=i.split("\n");if(1!=n.length)return"mdscnv file has multiple header lines (begin with #), but should have just 1";const r=n[0].split("\t");t.samples=r.slice(5),t.attributeSummary=be(t.samples,e),t.hierarchySummary=_e(t.samples,e);for(const e in t.hierarchySummary){let n=0;for(const r in t.hierarchySummary[e])n++;console.log(n+" "+e+" hierarchy levels for "+t.name)}}{const e=p.execSync(vt+" -l "+r,o).trim();if(!e)return"no chromosomes found";t.nochr=k.contigNameNoChr(n,e.split("\n"))}console.log("("+t.type+") "+t.name+": "+(t.samples?t.samples.length:"no")+" samples, "+(t.nochr?'no "chr"':'has "chr"'))}function xe(t,e,n){let r;if(t.file){const[e,n]=se(t.file);if(e)return"tabix file error: "+e;r=n}else{if(!t.url)return"no file or url given for (svcnv) "+t.name;r=t.url}const o={encoding:"utf8"};const i=p.execSync(vt+" -H "+r,o).trim();if(i){const n=new Set;for(const t of i.split("\n"))for(const e of t.split(" ").slice(1))n.add(e);if(0==n.size)return"no samples from the header line";if(t.samples=[...n],e.cohort&&e.cohort.annotation){const n=new Set;for(const r of t.samples)e.cohort.annotation[r]||n.add(r);n.size&&console.log("mdssvcnv unannotated samples: "+(t.noprintunannotatedsamples?n.size:[...n].join(" ")))}}{const e=p.execSync(vt+" -l "+r,o).trim();if(!e)return"no chromosomes found";t.nochr=k.contigNameNoChr(n,e.split("\n"))}if(t.expressionrank_querykey){const n=e.queries[t.expressionrank_querykey];if(!n)return"invalid key by expressionrank_querykey";if(!n.isgenenumeric)return"query "+t.expressionrank_querykey+" not tagged as isgenenumeric"}if(t.vcf_querykey){const n=e.queries[t.vcf_querykey];if(!n)return"invalid key by vcf_querykey";if(n.type!=k.tkt.mdsvcf)return"query "+t.vcf_querykey+" not of mdsvcf type"}if(t.groupsamplebyattr){if(!t.groupsamplebyattr.attrlst)return".attrlst[] missing from groupsamplebyattr";if(0==t.groupsamplebyattr.attrlst.length)return"groupsamplebyattr.attrlst[] empty array";if(!e.cohort)return"groupsamplebyattr in use but ds.cohort missing";if(!e.cohort.annotation)return"groupsamplebyattr in use but ds.cohort.annotation missing";e.cohort.sampleAttribute||(e.cohort.sampleAttribute={}),e.cohort.sampleAttribute.attributes||(e.cohort.sampleAttribute.attributes={},console.log("cohort.sampleAttribute added when groupsamplebyattr is in use"));for(const n of t.groupsamplebyattr.attrlst){if(!n.k)return"k missing from one of groupsamplebyattr.attrlst[]";e.cohort.sampleAttribute.attributes[n.k]||(e.cohort.sampleAttribute.attributes[n.k]={label:n.label||n.k})}if(t.groupsamplebyattr.sortgroupby){if(!t.groupsamplebyattr.sortgroupby.key)return".key missing from .sortgroupby";if(!t.groupsamplebyattr.sortgroupby.order)return".order[] missing from .sortgroupby";if(!Array.isArray(t.groupsamplebyattr.sortgroupby.order))return".order must be an array"}t.groupsamplebyattr.attrnamespacer||(t.groupsamplebyattr.attrnamespacer=", ")}console.log("("+t.type+") "+t.name+": "+(t.samples?t.samples.length:"no")+" samples, "+(t.nochr?'no "chr"':'has "chr"'))}function ke(t,e,n){if(!t.datatype)return"datatype missing";if(t.viewrangeupperlimit&&Number.isNaN(t.viewrangeupperlimit))return"invalid value for viewrangeupperlimit";let r;if(!t.file)return"file missing";{const[e,n]=se(t.file);if(e)return"tabix file error: "+e;r=n}const o={cwd:null,encoding:"utf8"};{const e=p.execSync(vt+" -H "+r,o).trim();if(!e)return"no header line (#sample <sample1> ...)";const n=new Set;for(const t of e.split("\n")){const e=t.split(" ");for(let t=1;t<e.length;t++)n.add(e[t])}if(0==n.size)return"no sample names from header line";t.samples=[...n],console.log("(genenumeric) "+t.name+": "+t.samples.length+" samples")}if(t.boxplotbysamplegroup){if(!t.boxplotbysamplegroup.attributes)return"boxplotbysamplegroup.attributes missing";if(!Array.isArray(t.boxplotbysamplegroup.attributes))return"boxplotbysamplegroup.attributes should be array";for(const e of t.boxplotbysamplegroup.attributes)if(!e.k)return"k missing from one of boxplotbysamplegroup.attributes[]"}}async function qe(t,e,n){if(!t.tracks)return"tracks[] missing";if(!Array.isArray(t.tracks))return"tracks should be array";t.info={};for(const r of t.tracks){if(!r.file)return"file missing from a track (url not supported yet)";const[o,i]=se(r.file);if(o)return"tabix file error: "+o;if(r.type!=k.mdsvcftype.vcf)return"invalid track type: "+r.type;{r.cwd;const e=await x.get_header_tabix(i,r.cwd);if(0==e.length)return"no meta/header lines for "+i;const[n,o,s,a]=q.vcfparsemeta(e);if(a)return"error parsing vcf meta for "+i+": "+a.join("\n");if(0==s.length)return"vcf file has no sample: "+i;for(const e in n)t.info[e]=n[e];if(r.format=o,r.samplenameconvert){if("function"!=typeof r.samplenameconvert)return".samplenameconvert must be function";for(const t of s)t.name=r.samplenameconvert(t.name)}r.samples=s}if(e.cohort&&e.cohort.annotation){const t=[];for(const n of r.samples)e.cohort.annotation[n.name]||t.push(n.name);t.length&&console.log(e.label+": VCF "+r.file+" has unannotated samples: "+t.join(","))}{const t=[];if(await x.get_lines_bigfile({args:["-l",i],dir:r.cwd,callback:e=>{t.push(e)}}),0==t.length)return"no chr from "+i;r.nochr=k.contigNameNoChr(n,t)}console.log("("+t.type+") "+i+": "+r.samples.length+" samples, "+(r.nochr?"no chr":"has chr"))}if(t.singlesamples){if(!t.singlesamples.tablefile)return".singlesamples.tablefile missing for the VCF 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i=t.diff_score_plotwidth/(r-o),s=r*i-o*i,a=p(s*t.devicePixelRatio,e.canvasheight*t.devicePixelRatio),l=a.getContext("2d");t.devicePixelRatio>1&&l.scale(t.devicePixelRatio,t.devicePixelRatio);const c=n.map((t=>t.__tempscore)),u=e.canvasheight/c.length;let f=0;const d=e.stackspace/e.canvasheight;for(const t of c){let e=0;for(const n of t)"alt0"==n?l.fillStyle=Y:"ref"==n?l.fillStyle=nt:"alt1"==n?l.fillStyle=Q:"alt2"==n?l.fillStyle=K:"alt3"==n?l.fillStyle=X:"alt4"==n?l.fillStyle=tt:"alt5"==n&&(l.fillStyle=et),l.fillRect(i*e,f*u,i,u-d*u),e+=1;f+=1}return{height:e.canvasheight,width:s,src:a.toDataURL(),read_height:u}}function xt(t,e,n,r){for(const o of n)for(const n of o.segments)if(!(n.ridx!=t||Math.max(n.segstart,e.start)>Math.min(n.segstop,e.stop)))for(const t of n.boxes)if(e.ntwidth>=1){if(("S"==t.opr||"X"==t.opr)&&t.s)for(let e=0;e<t.s.length;e++){const n=t.start+e,o=r.find((t=>t.position==n));if(!o)continue;const i=t.s[e];o[i]=1+(o[i]||0),"S"==t.opr&&o.total++}}else if("S"==t.opr){const n=Math.floor((t.start-e.start)*e.ntwidth),o=Math.floor((t.start+t.len-e.start)*e.ntwidth);for(let t=n;t<=o;t++){const e=r[t];e&&(e.softclip=1+(e.softclip||0),e.total++)}}}async function kt(t,e){if(!await d.file_not_exist(e))return;if(!t.query.gdcFilePosition)throw".gdcFilePosition missing";const n=t.query.regions,r=t.query.gdcFilePosition.split(".");t.query.regions=[{chr:r[0],start:Number(r[1]),stop:Number(r[2])}],await Gt(t),t.query.regions=n}async function qt(t,e,n,r,o){const i=t.map((t=>t.segments[0].seq)),s=t.map((t=>t.segments[0].qual));let a="",l="";o&&(a+=">seq\n"+o.replace("\n","")+"\n");let c=0;for(const t of i){if(!(c<yt))break;a+=">seq\n"+t.replace("\n","")+"\n",l+=It(s[c].replace("\n",""))+"\n",c+=1}return await function(t,e,n,r,o,i,s,a){return new Promise(((n,l)=>{const c=m(k,["-i","-","-t","DNA","--outfmt=clu","--wrap=5000","--maxnumseq="+(e+1),"--maxseqlen=1000"]),u=[],d=[];f.from(t).pipe(c.stdin),c.stdout.on("data",(t=>u.push(t))),c.stderr.on("data",(t=>d.push(t))),c.on("error",(t=>{console.log("stderr (clustalo):",d),l(t)})),c.on("close",(t=>{let e=0;const c=[],f={final_read_align:[],qual_r:[],qual_g:[],qual_b:[]};let d=0;for(const t of u.toString().split("\n"))if(t.includes("seq ")){let n=0,l="",u=0,h="";0!=e&&a?h=r.split("\n")[e-1].split(","):a||(h=r.split("\n")[e].split(","));let p="",m="",g="";for(const r of t.replace("seq ",""))if(","!=r){if("-"!=r){if(n+=1,l+=r,0==e&&a)c.push(r);else if(r==c[u]&&a||!a){const t=S(h[n-1]/ft).replace("rgb(","").replace(")","").split(",");p+=t[0]+",",m+=t[1]+",",g+=t[2]+","}else if(r!=c[u]&&a){const t=E(h[n-1]/ft).replace("rgb(","").replace(")","").split(",");p+=t[0]+",",m+=t[1]+",",g+=t[2]+","}}else n>0&&n<t.replace(/-/g,"").replace(/,/g,"").replace("seq ","").length?(l+=r,0==e&&(c.push(r),u<o&&(d+=1))):(l+=" 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d.get_lines_bigfile({isbam:!0,args:n,dir:e.dir,callback:(n,r)=>{if(!(1024&n.split("\t")[1]&&e.drop_pcrduplicates)){if(e.downsample){const t=e.downsample;if(t.pointer++,t.pointer>=t.keep&&t.pointer<t.keep+t.skip)return;t.pointer>=t.keep+t.skip&&(t.pointer=0)}t.lines.push(n)}}})}async function At(t,e){const n=[],r=["depth","-r",(t.nochr?e.chr.replace("chr",""):e.chr)+":"+(e.start+1)+"-"+e.stop,"-g","DUP",t.file||t.url];if(t.drop_pcrduplicates&&(r.push("-G"),r.push("0x400")),await d.get_lines_bigfile({isbam:!0,args:r,dir:t.dir,callback:t=>{const r=t.split("\t"),o=Number.parseInt(r[1])-1,i=Number.parseInt(r[2]);if(e.ntwidth>=1)return void n.push({position:o,total:i});const s=Math.floor((o-e.start)*e.ntwidth);n[s]||(n[s]={position:o,sum:0,count:0}),n[s].sum+=i,n[s].count++}}),e.ntwidth<1)for(const t of n)t&&(t.total=t.sum/t.count,delete t.sum,delete t.count);return n}async function Mt(t,e){for(const t of e.regions)t.lines.length>0&&t.ntwidth>=st&&(t.to_checkmismatch=!0,t.referenceseq=await Et(e.genome,t.chr+":"+(t.start+1)+"-"+t.stop));for(const n of t)for(const t of n.segments){const n=e.regions[t.ridx];if(!n.to_checkmismatch)continue;const r=[];for(const e of t.boxes)null!=e.cidx&&"M"==e.opr&&(e.s=t.seq.substr(e.cidx,e.len),Ft(r,n,e,e.s));r.length&&t.boxes.push(...r)}for(const t of e.regions)delete t.to_checkmismatch,delete t.referenceseq}function Tt(t,e){if(!t.asPaired){const n=[];for(let r=0;r<t.regions.length;r++){const o=t.regions[r];for(const i of e.templates){i.ridx=r;const e=Ct(i,o,t);e&&n.push({x1:e.x1,x2:e.x2,__tempscore:e.tempscore,segments:[e]})}}return n}const n=new Map;for(let r=0;r<t.regions.length;r++){const o=t.regions[r];for(const i of e.templates){i.ridx=r;const e=Ct(i,o,t);if(!e||!e.qname)continue;const s=n.get(e.qname);s?(s.segments.push(e),s.x2=Math.max(s.x2,e.x2)):n.set(e.qname,{x1:Math.max(e.x1,o.x),x2:Math.min(e.x2,o.x+o.width),__tempscore:e.tempscore,segments:[e]})}}return[...n.values()]}function Ct(t,e,n){const{sam_info:r,tempscore:o,ridx:i,keepallboxes:s,keepmatepos:a,keepunmappedread:l}=t,c=r.trim().split("\t");if(c.length<11)return;const u=c[0],f=c[1],d=Number.parseInt(c[3]),h=c[5],p=c[6],m=c[7],g=Number.parseInt(c[8]),y=c[9],v=c[10];if(Number.isNaN(d)||d<=0)return;const b=d-1,_={qname:u,segstart:b,segstart_original:b,segstop:b,boxes:[],forward:!(16&f),ridx:i,seq:y,qual:v,cigarstr:h,tlen:g,flag:f,tempscore:o};if(function(t,e,n,r,o,i){const s=t.flag;if(!(1&s))return;64&s?t.isfirst=!0:128&s&&(t.islast=!0);if("="!=e&&"*"!=e&&e!=r.chr)return t.rnext=e,void(t.pnext=n);if(8&s)return void(t.discord_unmapped2=!0);32&s&&!(16&s)&&64&s||16&s&&!(32&s)&&128&s||16&s&&!(32&s)&&64&s||32&s&&!(16&s)&&128&s||(t.discord_orientation=!0,o&&(16&s?32&s?t.discord_orientation_direction="R1R2":n>i&&(t.discord_orientation_direction="R1F2"):32&s?n<i&&(t.discord_orientation_direction="R1F2"):t.discord_orientation_direction="F1F2")),2&s||(t.discord_wrong_insertsize=!0,o&&(t.pnext=n))}(_,p,m,e,a,d),4&f)return l?(_.boxes.push({opr:h,start:b,len:y.length,cidx:0,qual:v}),_.discord_unmapped1=!0,_):void 0;if("*"!=h){let t=b,r=0,o=0;for(let n=0;n<h.length;n++){const i=h[n];if(i.match(/[0-9]/))continue;const a=Number.parseInt(h.substring(r,n));if("H"!=i)if("N"==i||"P"==i||"D"==i||(o+=a),r=n+1,"="!=i&&"M"!=i)if("I"!=i)if("N"!=i&&"D"!=i)if("X"!=i)if("S"!=i){if("P"!=i)console.log("unknown cigar: "+i);else if(s||t>e.start&&t<e.stop){const e={opr:"P",start:t,len:a,cidx:o-a};_.boxes.push(e)}}else{const n={opr:i,start:t,len:a,cidx:o-a};0==_.boxes.length?(n.start-=a,(s||Math.max(t,e.start)<=Math.min(t+a-1,e.stop))&&_.boxes.push(n)):_.boxes.push(n)}else{if(s||Math.max(t,e.start)<Math.min(t+a-1,e.stop)){const e={opr:i,start:t,len:a,cidx:o-a};_.boxes.push(e)}t+=a}else(t>=e.start&&t<=e.stop||t+a-1>=e.start&&t+a-1<=e.stop||s)&&_.boxes.push({opr:i,start:t,len:a}),t+=a;else(s||t>e.start&&t<e.stop)&&a*e.ntwidth>=rt&&_.boxes.push({opr:"I",start:t,len:a,cidx:o-a});else(s||Math.max(t,e.start)<=Math.min(t+a-1,e.stop))&&_.boxes.push({opr:i,start:t,len:a,cidx:o-a}),t+=a;else _.boxes.push({opr:i,start:t,len:a,cidx:o-a}),r=n+1}if(0==_.boxes.length)return void(n&&n.readcount_skipped++);_.segstop=t,_.x1=e.x+e.scale(_.boxes[0].start),_.x2=e.x+e.scale((w=_.boxes,Math.max(...w.map((t=>t.start+t.len)))))}var w;return _}async function jt(t,e,n){const[r,o]=function(t,e){let n=(e.groups.length>1?pt/2:pt)/t;return n>10?[Math.min(15,Math.floor(n)),1]:n>7?[Math.floor(n),1]:n>3?[Math.ceil(n),0]:n>1?[Math.floor(n),0]:[n,0]}(t.stacks.length,e);t.stackheight=r,t.stackspace=o;for(const e of t.regions)e.to_printnt=t.stackheight>7&&e.ntwidth>=7,e.to_qual=e.ntwidth>=ot;if(t.stacks.length&&(t.stackheight>=gt&&n.length<mt?t.returntemplatebox=[]:t.partstack||(t.allowpartstack=!0)),t.stackheight>=at){let e=0;for(const t of n)for(const n of t.segments)e=Math.max(e,n.x2-n.x1);e>.7*t.stackheight&&(t.canClipArrowhead=!0)}}function Ot(t,e,n){if(e.asPaired){t.stacks=[];const r=[],o=[];for(const t of n){let n=t.segments[0].ridx;1==t.segments.length||2==t.segments.length&&t.segments[0].ridx==t.segments[1].ridx?(t.x1=Math.max(e.regions[n].x,t.x1),t.x2=Math.min(e.regions[n].x+e.regions[n].width,t.x2),r.push(t)):2==t.segments.length&&t.segments[0].ridx!=t.segments[1].ridx&&(t.x1=t.x1,t.x2=t.x2,o.push(t))}if(r.sort(((t,e)=>t.x1-e.x1)),o.sort(((t,e)=>t.x1-e.x1)),o.length>0){const t=[],e=[],i=o[0];for(const n of r)n.x1<i.x1&&n.x2<i.x1?t.push(n):e.push(n);n=[...t,...o,...e]}for(const r of n){let n=r.segments[0].ridx,o=null;if(!e.variant)for(let i=0;i<t.stacks.length;i++){if(r.x2==e.regions[n].x+e.regions[n].width&&t.stacks[i]<r.x1){o=i,t.stacks[i]=r.x2;break}if(t.stacks[i]+e.stacksegspacing<r.x1){o=i,t.stacks[i]=r.x2;break}}null==o&&(o=t.stacks.length,t.stacks[o]=r.x2),r.y=o}}else{n.sort(((t,e)=>t.x1-e.x1)),t.stacks=[];for(let r=0;r<e.regions.length;r++)for(const o of n)if(o.segments[0].ridx==r){let n=null;if(!e.variant&&!e.sv)for(let i=0;i<t.stacks.length;i++)if(t.stacks[i]+e.stacksegspacing<o.x1&&t.stacks[i]+e.stacksegspacing<e.regions[r].x+e.regions[r].width){n=i,t.stacks[i]=o.x2;break}null==n&&(n=t.stacks.length,t.stacks[n]=o.x2),o.y=n}}return n=function(t,e,n){if(!t.partstack)return e;const r=e.filter((e=>e.y>=t.partstack.start&&e.y<=t.partstack.stop));r.forEach((e=>e.y-=t.partstack.start)),e=r,t.stacks=[];for(let e=t.partstack.start;e<=t.partstack.stop;e++)t.stacks.push(0);return 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e.seq,delete e.qual}}}function It(t){if("*"==t)return null;const e=[];for(let n=0;n<t.length;n++){const r=t[n].charCodeAt(0)-33;e.push(r)}return e}function Pt(t,e){if(2==t.segments.length){const[n,r]=t.segments;return n.x2>r.x1?(r.shiftdownrow=1,2*e):e}console.log("more than 2 segments",t.segments.length);const n=[];for(const e of t.segments){let t=null;for(let r=0;r<n.length;r++)if(n[r]<e.x1){t=r,n[r]=e.x2;break}null==t&&(t=n.length,n[t]=e.x2),e.shiftdownrow=t}return e*n.length}function Ft(t,e,n,r){for(let o=0;o<r.length;o++){if(n.start+o<e.start||n.start+o>e.stop)continue;const i=r[o];if(e.referenceseq[n.start+o-e.start]!=i.toUpperCase()){const e={opr:"X",start:n.start+o,len:1,s:i,cidx:n.cidx+o};t.push(e)}}}function Lt(t,e,n,r){if(n.returntemplatebox){const t=n.regions[e.segments[0].ridx];let 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o={qname:e.segments[0].qname,x1:Math.max(t.x,e.x1),x2:Math.min(e.x2,t.x+t.width),y1:e.y,y2:e.y+(e.height||n.stackheight),start:Math.min(...e.segments.map((t=>t.segstart))),stop:Math.max(...e.segments.map((t=>t.segstop)))},e.segments[0].isfirst&&(o.isfirst=!0),e.segments[0].islast&&(o.islast=!0);n.returntemplatebox.push(o)}for(let o=0;o<e.segments.length;o++){const i=e.segments[o],s=n.regions[i.ridx];if(s.width=n.widths[i.ridx],0==o){Dt(t,i,e.y,n,r);continue}const a=e.segments[o-1],l=n.regions[a.ridx];if(l.width=n.widths[a.ridx],a.x2<=i.x1||e.segments[0].ridx!=e.segments[1].ridx){Dt(t,i,e.y,n,r);const o=Math.floor(e.y+n.stackheight/2)+.5;if(t.strokeStyle=n.stackheight<=2?W:q,t.setLineDash([5,3]),t.beginPath(),l.x==s.x?(t.moveTo(a.x2,o),t.lineTo(i.x1,o)):l.x<a.x2&&i.x1<s.width&&(t.moveTo(Math.min(a.x2,l.width),o),t.lineTo(Math.max(i.x1,s.x),o)),t.stroke(),n.overlapRP_hlline){const r=a.boxes.reduce(((t,e)=>t.start+t.len>e.start+e.len?t:e));if(r.start+r.len==i.boxes[0].start){t.strokeStyle=H,t.setLineDash([]),t.beginPath();const r=Math.floor(i.x1)+.5;t.moveTo(r,e.y),t.lineTo(r,e.y+n.stackheight),t.stroke()}}}else if(n.overlapRP_multirows){if(Dt(t,i,e.y+n.stackheight,n,r),n.overlapRP_hlline){const r=Math.floor(e.y+n.stackheight)+.5;t.strokeStyle=H,t.setLineDash([]),t.beginPath(),l.x<=a.x2&&i.x1<=s.width&&(t.moveTo(Math.max(i.x1,s.x),r),t.lineTo(Math.min(a.x2,l.width),r)),t.stroke()}}else Dt(t,i,e.y,n,r)}null!=e.__tempscore&&x.features.indel_read_alignment_scores&&(t.fillStyle="blue",t.font=n.stackheight+"pt Arial",t.fillText(e.__tempscore,r.regions[0].width-100,e.y+n.stackheight/2))}function Dt(t,e,n,r,o){const i=r.regions[e.ridx];i.width=r.widths[e.ridx];for(const o of e.boxes){const s=i.x+i.scale(o.start);if("P"!=o.opr&&"H"!=o.opr&&"I"!=o.opr)if("D"!=o.opr&&"N"!=o.opr)if("*"!=o.opr){if("X"!=o.opr&&"S"!=o.opr){if("M"!=o.opr&&"="!=o.opr)throw"unknown opr at 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o.qual?e.rnext?t.fillStyle=A:e.discord_orientation?t.fillStyle=D:e.discord_wrong_insertsize?t.fillStyle=T:e.discord_unmapped2?t.fillStyle=F:t.fillStyle=q:i.to_printnt?t.fillStyle="white":e.rnext?t.fillStyle=A:e.discord_orientation?t.fillStyle=D:e.discord_wrong_insertsize?t.fillStyle=T:e.discord_unmapped2?t.fillStyle=F:t.fillStyle=q,s+o.len*i.ntwidth+dt<i.width&&s<i.width&&i.x<s+dt?t.fillRect(s,n,o.len*i.ntwidth+dt,r.stackheight):s+o.len*i.ntwidth+dt<i.width&&i.x>=s?t.fillRect(i.x,n,o.len*i.ntwidth+dt+s-i.x,r.stackheight):s+o.len*i.ntwidth+dt>=i.width&&i.x<s?t.fillRect(s,n,i.width-s,r.stackheight):s+o.len*i.ntwidth+dt>=i.width&&i.x>=s&&t.fillRect(i.x,n,i.width-s,r.stackheight);if(i.to_printnt){t.font=Math.min(i.ntwidth,r.stackheight-2)+"pt Arial",o.qual?t.fillStyle="white":t.fillStyle="black";for(let e=0;e<o.s.length;e++)s+i.ntwidth*(e+.5)<i.width&&s<i.width&&i.x<=s+i.ntwidth*(e+.5)&&t.fillText(o.s[e],s+i.ntwidth*(e+.5),n+r.stackheight/2)}}else if(i.to_qual&&o.qual){i.to_printnt&&(t.font=Math.min(i.ntwidth,r.stackheight-2)+"pt Arial");let e=s;for(let s=0;s<o.qual.length;s++){const a=o.qual[s]/ft;t.fillStyle="S"==o.opr?P(a):E(a),e+i.ntwidth+dt<i.x+i.width&&i.x<=e?t.fillRect(e,n,i.ntwidth+dt,r.stackheight):e<i.x+i.width&&e+i.ntwidth+dt>=i.x+i.width&&i.x<=e?t.fillRect(e,n,i.width+i.x-e,r.stackheight):e<=i.x&&e+i.ntwidth+dt>i.x&&t.fillRect(i.x,n,i.ntwidth+dt+e-i.x,r.stackheight),i.to_printnt&&(o.qual?t.fillStyle="white":t.fillStyle="black",e+i.ntwidth/2<i.width&&e<i.width&&i.x<=e+i.ntwidth/2&&t.fillText(o.s[s],e+i.ntwidth/2,n+r.stackheight/2)),e+=i.ntwidth}}else if(t.fillStyle="S"==o.opr?R:j,s+o.len*i.ntwidth+dt<i.width&&i.x<s?t.fillRect(s,n,o.len*i.ntwidth+dt,r.stackheight):s+o.len*i.ntwidth+dt<i.width&&i.x>=s?t.fillRect(i.x,n,o.len*i.ntwidth+dt+s-i.x,r.stackheight):s+o.len*i.ntwidth+dt<=i.width&&i.x<s&&t.fillRect(s,n,i.width-s,r.stackheight),i.to_printnt&&!o.qual){t.font=Math.min(i.ntwidth,r.stackheight-2)+"pt Arial",o.qual?t.fillStyle="white":t.fillStyle="black";for(let e=0;e<o.s.length;e++)s+i.ntwidth*(e+.5)<i.width&&s<i.width&&i.x<=s+i.ntwidth*(e+.5)&&t.fillText(o.s[e],s+i.ntwidth*(e+.5),n+r.stackheight/2)}}else{if(i.to_qual&&o.qual){let a=s;o.qual.forEach((o=>{e.discord_unmapped2&&(t.fillStyle=L(o/ft)),t.fillRect(a,n,i.ntwidth+dt,r.stackheight),a+=i.ntwidth}))}else e.discord_unmapped2&&(t.fillStyle=F),t.fillRect(s,n,o.len*i.ntwidth+dt,r.stackheight);i.to_printnt&&(t.font=Math.min(i.ntwidth,r.stackheight-2)+"pt Arial")}else{"D"==o.opr?t.strokeStyle=J:t.strokeStyle=r.stackheight<=2?W:q,t.setLineDash([]);const e=Math.floor(n+r.stackheight/2)+.5;if(t.beginPath(),t.moveTo(Math.max(s,i.x),e),t.lineTo(Math.min(s+o.len*i.ntwidth,i.x+i.width),e),t.stroke(),r.stackheight>lt){const e=Math.max(i.x,s),a=Math.min(i.x+i.width,s+o.len*i.ntwidth);if(a-e>=50){const s=Math.min(ct,Math.max(ut,r.stackheight-2));t.font=s+"pt Arial";const l=t.measureText(o.len+" bp").width;l<a-e-20&&(t.fillStyle="white",(a+e)/2+l/2<i.width&&i.x<(a+e)/2-l/2?(t.fillRect((a+e)/2-l/2,n,l,r.stackheight),t.fillStyle=q,t.fillText(o.len+" bp",(a+e)/2,n+r.stackheight/2)):(a+e)/2+l/2<i.width&&i.x>=(a+e)/2-l/2?(t.fillRect(i.x,n,l+(a+e)/2-l/2-i.x,r.stackheight),t.fillStyle=q,t.fillText(o.len+" bp",(a+e)/2,n+r.stackheight/2)):(a+e)/2+l/2>=i.width&&i.x<(a+e)/2-l/2&&(t.fillRect((a+e)/2-l/2,n,i.width-(a+e)/2+l/2,r.stackheight),t.fillStyle=q,t.fillText(o.len+" bp",(a+e)/2,n+r.stackheight/2)))}}}}!function(t,e,n,r,o){if(!n.canClipArrowhead)return;if(e.x2-e.x1<5)return;if(e.forward){const i=Math.ceil(e.x2+dt);i<=r.width+n.stackheight/2&&(t.fillStyle="white",t.beginPath(),t.moveTo(i-n.stackheight/2,o),t.lineTo(i,o),t.lineTo(i,o+n.stackheight/2),t.lineTo(i-n.stackheight/2,o),t.closePath(),t.fill(),t.beginPath(),t.moveTo(i-n.stackheight/2,o+n.stackheight),t.lineTo(i,o+n.stackheight),t.lineTo(i,o+n.stackheight/2),t.lineTo(i-n.stackheight/2,o+n.stackheight),t.closePath(),t.fill())}else{const i=e.x1;i>=r.x&&(t.fillStyle="white",t.beginPath(),t.moveTo(i+n.stackheight/2,o),t.lineTo(i,o),t.lineTo(i,o+n.stackheight/2),t.lineTo(i+n.stackheight/2,o),t.closePath(),t.fill(),t.beginPath(),t.moveTo(i+n.stackheight/2,o+n.stackheight),t.lineTo(i,o+n.stackheight),t.lineTo(i,o+n.stackheight/2),t.lineTo(i+n.stackheight/2,o+n.stackheight),t.closePath(),t.fill())}}(t,e,r,i,n),e.rnext&&(i.to_qual||e.x2-e.x1>=20&&r.stackheight>=7&&(t.font=Math.min(G,Math.max(U,r.stackheight-4))+"pt Arial",t.fillStyle="white",t.fillText((o.nochr?"chr":"")+e.rnext,(e.x1+e.x2)/2,n+r.stackheight/2,e.x2-e.x1)))}function Bt(t,e,n,r){for(const[t,n]of e.regions.entries()){if(!n.to_printnt)continue;const e=new Set;for(const o of r)for(const r of o.segments){if(r.ridx!=t)continue;const o=r.boxes.filter((t=>"I"==t.opr));if(o.length)for(const t of o)e.add(n.x+n.scale(t.start))}}for(const n of r)for(const r of n.segments){const o=e.regions[r.ridx],i=r.boxes.filter((t=>"I"==t.opr));if(i.length){t.font=Math.max(G,e.stackheight-2)+"pt Arial";for(const s of i){const i=o.x+o.scale(s.start);s.qual?t.fillStyle=$(s.qual.reduce(((t,e)=>t+e),0)/s.qual.length/ft):t.fillStyle=z;const a=1==s.s.length?s.s:s.s.length;t.fillText(a,i,n.y+e.stackheight*(r.on2ndrow||0)+e.stackheight/2)}}}}async function zt(t,e,n){const r=It(t.qual),o=['<td style="color:black;text-align:left">Read</td>'];for(const e of t.boxes)for(let n=0;n<e.len;n++){t.seq[e.cidx+n];o.push('<td style="background:'+S(r[e.cidx+n]/ft)+'">'+t.seq[e.cidx+n]+"</td>")}const i=[];i.push('<li><span style="background:'+F+';color:white">This segment in template is unmapped</span></li>'),1&t.flag&&i.push("<li>Template has multiple segments</li>"),2&t.flag&&i.push("<li>Each segment properly aligned</li>"),16&t.flag&&i.push("<li>Reverse complemented</li>"),32&t.flag&&i.push("<li>Next segment in the template is reverse complemented</li>"),64&t.flag&&i.push("<li>This is the first segment in the template</li>"),128&t.flag&&i.push("<li>This is the last segment in the template</li>"),256&t.flag&&i.push("<li>Secondary alignment</li>"),512&t.flag&&i.push("<li>Not passing filters</li>"),1024&t.flag&&i.push("<li>PCR or optical duplicate</li>"),2048&t.flag&&i.push("<li>Supplementary alignment</li>");let s={seq:t.seq,alignment:`<table style="border-spacing:0px;border-collapse:separate;text-align:center">\n\t\t\t <tr style="color:white">${o.join("")}</tr>\n\t\t\t</table>`,info:`<div style='margin-top:10px'>\n\t\t\t<span style="opacity:.5;font-size:.7em">TEMPLATE</span>: ${Math.abs(t.seq.length)} bp,\n\t\t\t<span style="opacity:.5;font-size:.7em">CIGAR</span>: ${t.cigarstr}\n\t\t\t<span style="opacity:.5;font-size:.7em">FLAG</span>: ${t.flag}\n\t\t\t<span style="opacity:.5;font-size:.7em">NAME: ${t.qname}</span>\n\t\t </div>\n\t\t <ul style='padding-left:15px'>${i.join("")}</ul>`};return t.discord_unmapped2&&(s.unmapped_mate=!0),s}async function Zt(t,e,n){const r=t.boxes[0].start,o=t.boxes[t.boxes.length-1],i=o.start+o.len,s=await Et(e,n.chr+":"+(r+1)+"-"+i),a=It(t.qual),l=["<td>Reference</td>"],c=['<td style="color:black;text-align:left">Read</td>'];for(const e of t.boxes)if("H"!=e.opr)if("I"!=e.opr)if("D"!=e.opr&&"N"!=e.opr)if("S"!=e.opr)if("M"!=e.opr&&"="!=e.opr&&"X"!=e.opr&&"*"!=e.opr);else for(let n=0;n<e.len;n++){const o=s[e.start-r+n],i=t.seq[e.cidx+n];l.push("<td>"+o+"</td>"),"*"==t.qual?c.push('<td style="color:black;background:'+(o.toUpperCase()==i.toUpperCase()?S:E)+'">'+t.seq[e.cidx+n]+"</td>"):c.push('<td style="background:'+(o.toUpperCase()==i.toUpperCase()?S:E)(a[e.cidx+n]/ft)+'">'+t.seq[e.cidx+n]+"</td>")}else for(let n=0;n<e.len;n++)l.push("<td>"+s[e.start-r+n]+"</td>"),"*"==t.qual?c.push('<td style="background:'+P(1)+'">'+t.seq[e.cidx+n]+"</td>"):c.push('<td style="background:'+P(a[e.cidx+n]/ft)+'">'+t.seq[e.cidx+n]+"</td>");else if(e.len>=vt)l.push('<td style="font-size:.8em;opacity:.5;white-space:nowrap">'+e.len+" bp</td>"),c.push('<td style="color:black;white-space:nowrap">-----------</td>');else for(let t=0;t<e.len;t++)l.push("<td>"+s[e.start-r+t]+"</td>"),c.push('<td style="color:black">-</td>');else for(let n=e.cidx;n<e.cidx+e.len;n++)l.push("<td>-</td>"),"*"==t.qual?c.push('<td style="color:'+z+';background:white">'+t.seq[n]+"</td>"):c.push('<td style="color:'+z+";background:"+S(a[n]/ft)+'">'+t.seq[n]+"</td>");let u=0,f=0,d=[],h=[],p=0;for(const e of t.boxes)u=f,f+=e.len,"S"==e.opr&&(p=1,d.push(u),h.push(f));const m=[];t.rnext&&m.push('<li>Next segment on <span style="background:'+A+'">'+(n.nochr?"chr":"")+t.rnext+", "+t.pnext+"</span></li>"),t.discord_wrong_insertsize&&t.discord_orientation?m.push('<li><span style="background:'+T+';color:white">Wrong insert size</span> mate position: '+t.pnext+'</li><li><span style="background:'+D+';color:white">Segments also having wrong orientation</span> '+t.discord_orientation_direction+"</li>"):t.discord_wrong_insertsize?m.push('<li><span style="background:'+T+';color:white">Wrong insert size</span> mate position: '+t.pnext+"</li>"):t.discord_orientation?m.push('<li><span style="background:'+D+';color:white">Segments having wrong orientation</span> '+t.discord_orientation_direction+"</li>"):t.discord_unmapped2&&m.push('<li><span style="background:'+F+';color:white">Other segment in template is unmapped</span></li>'),1&t.flag&&m.push("<li>Template has multiple segments</li>"),2&t.flag&&m.push("<li>Each segment properly aligned</li>"),16&t.flag&&m.push("<li>Reverse complemented</li>"),32&t.flag&&m.push("<li>Next segment in the template is reverse complemented</li>"),64&t.flag&&m.push("<li>This is the first segment in the template</li>"),128&t.flag&&m.push("<li>This is the last segment in the template</li>"),256&t.flag&&m.push("<li>Secondary alignment</li>"),512&t.flag&&m.push("<li>Not passing filters</li>"),1024&t.flag&&m.push("<li>PCR or optical duplicate</li>"),2048&t.flag&&m.push("<li>Supplementary alignment</li>");let g={seq:t.seq,alignment:`<table style="border-spacing:0px;border-collapse:separate;text-align:center;font-family:courier">\n\t\t\t <tr style="opacity:.6">${l.join("")}</tr>\n\t\t\t <tr style="color:white">${c.join("")}</tr>\n\t\t\t</table>`,info:`<div style='margin-top:10px'>\n\t\t\t<span style="opacity:.5;font-size:.7em">CHR</span>: ${n.chr.replace("chr","")},\n\t\t\t<span style="opacity:.5;font-size:.7em">START</span>: ${t.segstart_original+1},\n\t\t\t<span style="opacity:.5;font-size:.7em">STOP</span>: ${i},\n\t\t\t<span style="opacity:.5;font-size:.7em">READ LENGTH</span>: ${t.seq.length} bp,\n\t\t\t<span style="opacity:.5;font-size:.7em">TEMPLATE LENGTH</span>: ${Math.abs(t.tlen)} bp,\n\t\t\t<span style="opacity:.5;font-size:.7em">CIGAR</span>: ${t.cigarstr}\n\t\t\t<span style="opacity:.5;font-size:.7em">FLAG</span>: ${t.flag}\n\t\t\t<span style="opacity:.5;font-size:.7em">NAME: ${t.qname}</span>\n\t\t </div>\n\t\t <ul style='padding-left:15px'>${m.join("")}</ul>`,start_readpos:r+1,boxes:t.boxes,readpanel_DN_maxlength:vt};return 1==p&&(g.soft_starts=d,g.soft_stops=h),t.discord_unmapped2&&(g.unmapped_mate=!0),g}function $t(t){const e=i.createHmac("md5",_t),n=[t.get("X-Auth-Token")||t.cookies.sessionid,t.query.gdcFileUUID,t.query.gdcFilePosition];return e.update(n.join("")).digest("hex")+".bam"}async function Gt(t){const e=t.query.regions;if(!Array.isArray(e)||0==e.length)throw"req.query.regions[] not non-empty array";const n=[];for(const r of e){const e=await Ut(r.chr,r.start,r.stop,t.get("X-Auth-Token"),t.query.gdcFileUUID,$t(t),t.cookies.sessionid);n.push({filesize:e})}return n}async function Ut(t,e,n,r,o,i,s){const f={compression:!1};s?f.Cookie=`sessionid=${s}`:f["X-Auth-Token"]=r;const h=c.join(x.cachedir_bam,i),p=bt+"/slicing/view/"+o+"?region="+t+":"+e+"-"+n;try{if(await d.file_not_exist(h)&&(await l(a.stream(p,{method:"GET",headers:f}),u.createWriteStream(h)),await d.file_not_exist(h)))throw"BAM file slice is not found after downloading";const t=h+".bai";if(await d.file_not_exist(t)&&(await async function(t){await d.get_lines_bigfile({isbam:!0,args:["index",t],callback:()=>{}})}(h),await d.file_not_exist(t)))throw"index file is missing after indexing";const e=await u.promises.stat(h);return _(e.size,!0)}catch(t){throw t.stack&&console.log(t.stack),"Error with BAM slicing: "+(t.message||t)}}t.exports=t=>async(e,n)=>{try{if(delete e.query.isFileSlice,e.query.gdcFileUUID){const t=e.cookies.sessionid,n=e.get("X-Auth-Token");if(!n&&!t)throw"GDC token or sessionid missing";await w(e.query.gdcFileUUID,n,t),e.query.file=$t(e),e.query.isFileSlice=!0}if(e.query.downloadgdc)return void n.send(await Gt(e));if(e.query.clientdownloadgdcslice){if(!e.query.file||!e.query.isFileSlice)throw"invalid query";const t=c.join(x.cachedir_bam,e.query.file),r=await u.promises.readFile(t);return n.writeHead(200,{"Content-Type":"application/octet-stream","Content-Disposition":"attachment; filename=gdc.bam","Content-Length":r.length}),void n.end(Buffer.from(r,"binary"))}if(!e.query.genome)throw".genome missing";const o=t[e.query.genome];if(!o)throw"invalid genome";if(e.query.getread)return void n.send(await async function(t,e){if(!e.query.chr)throw".chr missing";if(!e.query.qname)throw".qname missing";if(e.query.qname=decodeURIComponent(e.query.qname),!e.query.start)throw".start missing";if(!e.query.stop)throw".stop missing";const n={chr:e.query.chr,start:Number(e.query.start),stop:Number(e.query.stop),scale:()=>{},ntwidth:10};if(!Number.isInteger(n.start))throw".start not integer";if(!Number.isInteger(n.stop))throw".stop not integer";const o=await async function(t,e){let n,o,i,s,a,l,u,f,p;if(t.query.isFileSlice)a=c.join(x.cachedir_bam,t.query.file),await kt(t,a);else{if([s,a,l]=r.fileurl(t),s)throw s;i=l?await d.cache_index(a,t.query.indexURL||a+".bai"):null}if(t.query.unknownorder&&(u=Number(t.query.readstart),f=Number(t.query.readstop),Number.isNaN(u)||Number.isNaN(f)))throw"readstart/stop not provided for read with unknown order";if(await d.get_lines_bigfile({isbam:!0,args:["view",a,(t.query.nochr?t.query.chr.replace("chr",""):t.query.chr)+":"+e.start+"-"+e.stop],dir:i,callback:(r,i)=>{if(r.split("\t")[0]!=t.query.qname)return;const s=Ct({sam_info:r,keepallboxes:!0,keepmatepos:!0,keepunmappedread:!0},e);if(s&&(!t.query.show_unmapped||!s.discord_unmapped2))if(t.query.show_unmapped&&t.query.getfirst){if(s.islast)return i.kill(),void(p=[s])}else if(t.query.show_unmapped&&t.query.getlast){if(s.isfirst)return i.kill(),void(p=[s])}else if(t.query.getfirst){if(s.isfirst)return i.kill(),void(p=[s])}else if(t.query.getlast){if(s.islast)return i.kill(),void(p=[s])}else if(t.query.unknownorder){if(s.segstart==u&&s.segstop==f)return i.kill(),void(p=[s])}else if(s.isfirst?n=s:s.islast&&(o=s),n&&o)return i.kill(),void(p=[n,o])}}),p){if(t.query.altseqs){const e={query_seq:p[0].seq,refseqs:t.query.refseqs,altseqs:t.query.altseqs,cigar_seq:p[0].cigarstr,start_position:p[0].segstart,ref_positions:t.query.ref_positions,refalleles:t.query.refalleles,altalleles:t.query.altalleles},n=(await h("align",JSON.stringify(e))).split("\n");let r;for(let t of n)t.includes("Final_output:")?r=JSON.parse(t.replace("Final_output:","")):console.log(t);p.alignments=r}return p}p=[],n&&p.push(n);o&&p.push(o);return p.length?p:null}(e,n);if(!o){if(e.query.show_unmapped)throw"mate not found";throw"read not found"}const i=[];for(const n of o)n.discord_unmapped1?i.push(await zt(n,t,e.query)):i.push(await Zt(n,t,e.query));o.alignments&&(i[0].alignments=o.alignments);return{lst:i}}(o,e));const i=x.debugmode?new Date:null,s=await async function(t,e){let n;if(e.query.isFileSlice)n={genome:t,file:c.join(x.cachedir_bam,e.query.file),asPaired:e.query.asPaired,getcolorscale:e.query.getcolorscale,devicePixelRatio:e.query.devicePixelRatio?Number(e.query.devicePixelRatio):1},await kt(e,n.file);else{const[o,i,s]=r.fileurl(e);if(o)throw o;n={genome:t,file:i,asPaired:e.query.asPaired,getcolorscale:e.query.getcolorscale,devicePixelRatio:e.query.devicePixelRatio?Number(e.query.devicePixelRatio):1},s&&(n.dir=await d.cache_index(i,e.query.indexURL||i+".bai"))}if(e.query.pileupheight&&(n.pileupheight=Number(e.query.pileupheight),Number.isNaN(n.pileupheight)))throw".pileupheight is not integer";e.query.drop_pcrduplicates&&(n.drop_pcrduplicates=!0);if(e.query.variant){n.diff_score_plotwidth=Number(e.query.diff_score_plotwidth),e.query.max_diff_score&&(n.max_diff_score=Number(e.query.max_diff_score),n.min_diff_score=Number(e.query.min_diff_score));const t=e.query.variant.split(".");if(n.strictness=e.query.strictness,!Number.isInteger(t.length%4))throw"invalid variant, not chr.pos.ref.alt";n.alleleAlreadyUpdated=e.query.alleleAlreadyUpdated,n.alleleAlreadyUpdated&&(n.altseqs=e.query.altseqs,n.refseqs=e.query.refseqs,n.altalleles=e.query.altalleles,n.refalleles=e.query.refalleles,n.leftflankseqs=e.query.leftflankseqs,n.rightflankseqs=e.query.rightflankseqs,n.ref_positions=e.query.ref_positions);const r=t.length/4,o=[];for(let e=0;e<r;e++)o.push({chr:t[4*e],pos:Number(t[4*e+1]),ref:t[4*e+2],alt:t[4*e+3]});if(n.variant=o,e.query.alignOneGroup&&(n.alignOneGroup=e.query.alignOneGroup),Number.isNaN(n.variant.pos))throw"variant pos not integer"}else if(e.query.sv){const t=e.query.sv.split(".");if(t.length<6)throw"invalid sv, not chrA.posA.chrB.posB";if(n.sv={chrA:t[0],startA:Number(t[1]),strandA:Number(t[2]),chrB:t[3],startB:Number(t[4]),strandB:Number(t[5])},Number.isNaN(n.sv.startA))throw"sv.startA not integer";if(Number.isNaN(n.sv.startB))throw"sv.startB not integer"}if(Number.isFinite(Number(e.query.stackstart))){if(!e.query.stackstop)throw".stackstop missing";if(n.partstack={start:Number(e.query.stackstart),stop:Number(e.query.stackstop)},Number.isNaN(n.partstack.start))throw".stackstart not integer";if(Number.isNaN(n.partstack.stop))throw".stackstop not integer";if(!e.query.grouptype)throw".grouptype required for partstack";n.grouptype=e.query.grouptype}e.query.gdc||(e.query.nochr?n.nochr="string"==typeof e.query.nochr?JSON.parse(e.query.nochr):e.query.nochr:n.nochr=await d.bam_ifnochr(n.file,t,n.dir));if(n.regions=e.query.regions,!Array.isArray(n.regions)||0==n.regions.length)throw"q.regions[] not non-empty array";let o=0;for(const t of n.regions){if(!t.chr)throw".chr missing from a region";if(!Number.isInteger(t.start))throw".start not integer of a region";if(!Number.isInteger(t.stop))throw".stop not integer of a region";t.scale=e=>Math.ceil(t.width*(e-t.start)/(t.stop-t.start)),t.ntwidth=t.width/(t.stop-t.start),o=Math.max(o,t.ntwidth)}return n.stacksegspacing=Math.max(2,5*o),n.readcount_skipped=0,n}(o,e);n.send(await async function(t){await async function(t){if(t.variant){let e=0,n=0,r=0,o=t.variant[0].pos,i=t.variant[0].pos+Math.max(t.variant[0].ref.length,t.variant[0].alt.length);for(const s of t.variant){const t=Math.abs(s.pos-Math.max(s.ref.length,s.alt.length));t>e&&(e=t,n=r),o>s.pos&&(o=s.pos),i<s.pos+Math.max(s.ref.length,s.alt.length)&&(i=s.pos+Math.max(s.ref.length,s.alt.length)),r+=1}e=Math.floor(1.5*Math.max(t.variant[n].ref.length,t.variant[n].alt.length));const s={chr:t.variant[0].chr,start:o-e,stop:i+e};return await Nt(t,[s]),await St(s,t),void(t.regions[0].lines=s.lines)}await Nt(t,t.regions);for(const e of t.regions)await St(e,t)}(t),t.totalnumreads=t.regions.reduce(((t,e)=>t+e.lines.length),0);const e={nochr:t.nochr,count:{r:t.totalnumreads},groups:[]};t.read_limit_reached&&(e.count.read_limit_reached=t.read_limit_reached);t.canvaswidth=t.regions[t.regions.length-1].x+t.regions[t.regions.length-1].width;{const n=await async function(t){const e=[],n=[];let r=0;for(const o of t.regions){for(const t of o.lines)e.push({sam_info:t,tempscore:""});r=o.x+o.width,n.push(r)}if(0==e.length)return{groups:[{type:v.type_all,regions:v.duplicateRegions(t.regions),templates:e,messages:[],partstack:t.partstack,widths:n}]};if(t.variant){if(1==t.regions.length)return await y(t,e,n);console.log("Indel pipeline works only in single region. Please check!")}if(t.sv&&t.regions.length>1)return async function(t,e,n){const r=v.make_type2group(e),o=[];for(let t=0;t<e.regions.length;t++){const n=e.regions[t],r=(await d.get_fasta(e.genome,n.chr+":"+n.start+"-"+n.stop)).split("\n").slice(1).join("").toUpperCase(),i=[];for(const e of n.lines)i.push({sam_info:e,tempscore:"",ridx:t});const s={refseq:r,start:n.start,stop:n.stop,entries:i};0==t?(s.chr=e.sv.chrA,s.pos=e.sv.startA):1==t?(s.chr=e.sv.chrB,s.pos=e.sv.startB):console.log("More than two regions, please check"),o.push(s)}const i=new Date,s=(await h("sv",JSON.stringify(o))).split("\n"),a=new Date;let l,c;console.log("Time taken to run rust SV pipeline:",a-i,"ms");for(let t of s)t.includes("multi_region_templates:")?l=JSON.parse(t.replace("multi_region_templates:","")):t.includes("single_region_templates:")&&(c=JSON.parse(t.replace("single_region_templates:","")));if(!e.grouptype||"support_sv"==e.grouptype)for(const t of l)r[v.type_supportsv].templates.push(t);if(!e.grouptype||"support_ref"==e.grouptype)for(const t of c)r[v.type_supportref].templates.push(t);const u=[];for(const t in r){const e=r[t];0!=e.templates.length&&(t==v.type_supportsv?1==e.templates.length?e.messages.push({isheader:!0,t:e.templates.length+" read supporting SV/fusion"}):e.messages.push({isheader:!0,t:e.templates.length+" reads supporting SV/fusion"}):t==v.type_supportref&&e.messages.push({isheader:!0,t:e.templates.length+" reads supporting reference allele"}),e.widths=n,u.push(e))}return{groups:u}}(0,t,n);return{groups:[{type:v.type_all,regions:v.duplicateRegions(t.regions),templates:e,messages:[],partstack:t.partstack,widths:n}]}}(t);t.groups=n.groups,t.variant&&(e.ref_alleles=n.refalleles,e.alt_alleles=n.altalleles,e.allele_positions=n.ref_positions,e.strand_probability=n.strand_probability,e.alternate_forward_count=n.alternate_forward_count,e.reference_forward_count=n.reference_forward_count,e.alternate_reverse_count=n.alternate_reverse_count,e.reference_reverse_count=n.reference_reverse_count,1==n.strand_significance&&(e.strand_significance=!0),t.alleleAlreadyUpdated||(e.refseqs=n.refseqs,e.altseqs=n.altseqs,e.leftflankseqs=n.leftflankseqs,e.rightflankseqs=n.rightflankseqs,e.ref_positions=n.ref_positions,e.refalleles=n.refalleles,e.altalleles=n.altalleles)),Number.isFinite(t.max_diff_score)&&t.variant?(e.max_diff_score=t.max_diff_score,e.min_diff_score=t.min_diff_score):Number.isFinite(n.max_diff_score)&&(e.max_diff_score=n.max_diff_score,e.min_diff_score=n.min_diff_score),n.refalleleerror&&(e.refalleleerror=n.refalleleerror)}if(0==e.count.r)throw"No reads in view range.";if(t.alignOneGroup){const e=t.groups.find((e=>e.type==t.alignOneGroup));if(!e)throw"cannot find group for realignment";let n=Tt(t,e);return n=Ot(e,t,n),await async function(t,e,n){let r;if(e.variant)if("support_ref"==t.type){let o=e.leftflankseqs[0].length;r=t.partstack?await qt(n,o,t.partstack.start,t.partstack.stop,e.refseqs[0]):await qt(n,o,0,0,e.refseqs[0])}else if("support_no"==t.type){let o=e.leftflankseqs[0].length;r=t.partstack?await qt(n,o,t.partstack.start,t.partstack.stop):await qt(n,o)}else if("support_amb"==t.type)console.log("Realignment of reads in ambiguous group is not currently implemented");else if(t.type.includes("support_alt")){for(let o=0;o<e.variant.length;o++)if(t.type=="support_alt"+o.toString()){let i=e.leftflankseqs[o].length;r=t.partstack?await qt(n,i,t.partstack.start,t.partstack.stop,e.altseqs[o]):await qt(n,i,0,0,e.altseqs[o])}}else console.log("Unaccounted group, please check");return{alignmentData:r}}(e,t,n)}let n=[];for(const r of t.groups){let o=Tt(t,r);o=Ot(r,t,o),await jt(r,t,o),await Mt(o,t),Rt(r,o,t);const i={type:r.type,width:t.canvaswidth,height:r.canvasheight,stackheight:r.stackheight,stackcount:r.stacks.length,allowpartstack:r.allowpartstack,templatebox:r.returntemplatebox,count:{r:o.reduce(((t,e)=>t+e.segments.length),0)}},s=p(t.canvaswidth*t.devicePixelRatio,r.canvasheight*t.devicePixelRatio),a=s.getContext("2d");t.devicePixelRatio>1&&a.scale(t.devicePixelRatio,t.devicePixelRatio),a.textAlign="center",a.textBaseline="middle",i.messages=r.messages,i.messagerowheights=0;for(const e of o)Lt(a,e,r,t);Bt(a,r,t,o),t.asPaired&&(i.count.t=o.length),t.variant&&(i.diff_scores_img=await wt(t,r,o,e.max_diff_score,e.min_diff_score),"support_alt0"==i.type?i.group_color=Y:"support_alt1"==i.type?i.group_color=Q:"support_alt2"==i.type?i.group_color=K:"support_alt3"==i.type?i.group_color=X:"support_alt4"==i.type?i.group_color=tt:"support_alt5"==i.type?i.group_color=et:"support_ref"==i.type&&(i.group_color=nt)),i.src=s.toDataURL(),e.groups.push(i),n=[...n,...o]}t.readcount_skipped&&(e.count.skipped=t.readcount_skipped);t.getcolorscale&&(e.colorscale=function(t){const e=160,n=20,r=1,o=12,i=5,s=100,a=4,l=s+e+10,c=2*o+i+a+4*(n+r),u=p(t.devicePixelRatio*l,t.devicePixelRatio*c),f=u.getContext("2d");t.devicePixelRatio>1&&f.scale(t.devicePixelRatio,t.devicePixelRatio);f.fillStyle="black",f.font=o+"pt Arial",f.textAlign="center",f.fillText("Base quality",s+e/2,o);let d=2*o+i;function h(t,r,o){const i=s,a=f.createLinearGradient(i,o,i+e,o);a.addColorStop(0,r),a.addColorStop(1,t),f.fillStyle=a,f.fillRect(i,o,e,n)}return f.strokeStyle="black",f.beginPath(),f.moveTo(s,d),f.lineTo(s,d+a),f.moveTo(s+e/4,d),f.lineTo(s+e/4,d+a),f.moveTo(s+e/2,d),f.lineTo(s+e/2,d+a),f.moveTo(s+3*e/4,d),f.lineTo(s+3*e/4,d+a),f.moveTo(s+e,d),f.lineTo(s+e,d+a),f.closePath(),f.stroke(),f.fillText(40,s,d),f.fillText(30,s+e/4,d),f.fillText(20,s+e/2,d),f.fillText(10,s+3*e/4,d),f.fillText(0,s+e,d),f.textAlign="left",f.textBaseline="middle",d+=a,f.fillText("Match",0,d+n/2),h(N,q,d),d+=n+r,f.fillStyle="black",f.fillText("Mismatch",0,d+n/2),h(O,j,d),d+=n+r,f.fillStyle="black",f.fillText("Softclip",0,d+n/2),h(I,R,d),d+=n+r,f.fillStyle="black",f.fillText("Insertion",0,d+n/2),h(Z,z,d),{width:l,height:c,src:u.toDataURL()}}(t));if(!t.partstack)if(0==e.count.r);else{if(!t.pileupheight)throw"pileupheight missing";e.pileup_data=await async function(t,e){const n=p(t.canvaswidth*t.devicePixelRatio,t.pileupheight*t.devicePixelRatio),r=n.getContext("2d");t.devicePixelRatio>1&&r.scale(t.devicePixelRatio,t.devicePixelRatio);const o=[];let i=0;for(const[n,r]of t.regions.entries()){o[n]=await At(t,r),xt(n,r,e,o[n]);for(const t of o[n])t&&(i=Math.max(i,t.total))}for(const[e,n]of t.regions.entries()){const s=t.pileupheight/i;for(const i of o[e]){if(!i)continue;const e=(i.position-n.start)*n.ntwidth+n.x,o=n.ntwidth>=1?e:Math.floor(e),a=Math.max(1,n.ntwidth);{r.fillStyle=V;const e=i.total*s;r.fillRect(o,t.pileupheight-e,a,e)}let l=0;if(i.A){r.fillStyle=b.A;const e=i.A*s;r.fillRect(o,t.pileupheight-l-e,a,e),l+=e}if(i.C){r.fillStyle=b.C;const e=i.C*s;r.fillRect(o,t.pileupheight-l-e,a,e),l+=e}if(i.G){r.fillStyle=b.G;const e=i.G*s;r.fillRect(o,t.pileupheight-l-e,a,e),l+=e}if(i.T){r.fillStyle=b.T;const e=i.T*s;r.fillRect(o,t.pileupheight-l-e,a,e),l+=e}if(i.softclip){r.fillStyle=R;const e=i.softclip*s;r.fillRect(o,t.pileupheight-l-e,a,e)}}}return{width:t.canvaswidth,maxValue:i,src:n.toDataURL()}}(t,n)}return e}(s)),x.debugmode&&console.log("bam.js time ms",new Date-i)}catch(t){n.send({error:t.message||t}),t.stack&&console.log(t.stack)}}},8953:(t,e,n)=>{"use strict";n.d(e,{Y:()=>s});n(8171).jStat,n(1017),n(9699).features;const r=n(3856),o=n(1271).run_rust,i=(n(2081).spawn,n(2781).Readable,n(4521),n(2384));n(7147),n(334).clustalo;async function s(t,e,n){const s=t.regions[0].lines[0].split("\t")[9].length;let a=!1,l=[],c=[],u=[],f=[],d=[],h=[],p=[];if(t.alleleAlreadyUpdated)l=t.leftflankseqs,c=t.rightflankseqs,h=t.refseqs,p=t.altseqs,u=t.refalleles,f=t.altalleles,d=t.ref_positions,0!=h[0].toUpperCase().localeCompare((l[0]+u[0]+c[0]).toUpperCase())&&(console.log("Reference allele is not correct for variant 0"),a=!0);else{let e,n,o=0;for(const i of t.variant){let a="",l="";if(!(0!=i.ref.length&&"-"!=i.ref||"-"!=i.alt&&0!=i.alt.length))throw"Both Ref and Alt alleles are missing";if(0==i.ref.length||"-"==i.ref)a=(await r.get_fasta(t.genome,i.chr+":"+i.pos+"-"+i.pos)).split("\n").slice(1).join("").toUpperCase(),l=a+i.alt,i.pos-=1;else if("-"==i.alt||0==i.alt.length){const e=(await r.get_fasta(t.genome,i.chr+":"+i.pos+"-"+i.pos)).split("\n").slice(1).join("").toUpperCase();a=e+i.ref,l=e,i.pos-=1}else l=i.alt,a=i.ref;const c=i.pos,h=a.toUpperCase(),p=l.toUpperCase();0==o?(e=c-s,n=c+a.length+1+s):(c-s<e&&(e=c-s),c+a.length+1+s>n&&(n=c+a.length+1+s)),u.push(h),f.push(p),d.push(c),o+=1}o=0;for(const i of t.variant){const s=(await r.get_fasta(t.genome,i.chr+":"+e+"-"+d[o])).split("\n").slice(1).join("").toUpperCase(),a=(await r.get_fasta(t.genome,i.chr+":"+(d[o]+u[o].length+1)+"-"+n)).split("\n").slice(1).join("").toUpperCase(),m=s+u[o]+a,g=s+f[o]+a;console.log(i.chr+"."+d[o]+"."+u[o]+"."+f[o]),o+=1,l.push(s),c.push(a),h.push(m),p.push(g)}}const m=[];for(let t=0;t<e.length;t++){const n=e[t].sam_info.split("\t");m.push({read_sequence:n[9],start_position:Number(n[3]),cigar:n[5],flag:Number(n[1])})}const g=[];for(let t=0;t<u.length;t++)g.push({ref_position:Number(d[t]),refallele:u[t],altallele:f[t],refseq:h[t],altseq:p[t],leftflankseq:l[t],rightflankseq:c[t]});Number.isFinite(Number(t.strictness))||(t.strictness=1);const y={reads:m,alleles:g,strictness:Number(t.strictness)},v=new Date,b=await o("indel",JSON.stringify(y)),_=new Date;console.log("Time taken to run rust indel pipeline:",_-v,"ms");const w=b.split("\n");let x,k,q,N,S,A,M=0;for(let t of w)t.includes("Final_output:")?x=JSON.parse(JSON.parse(t.replace("Final_output:",""))):1==u.length&&t.includes("fisher_strand:")?(k=JSON.parse(t.replace("fisher_strand:","")),q=k.alternate_forward_count,N=k.alternate_reverse_count,S=k.reference_forward_count,A=k.reference_reverse_count,M=k.p_value):console.log(t);let T=!1;1==t.variant.length&&M>60&&(T=!0);const C=i.make_type2group(t);t.variant.length;let j=1;for(let n=0;n<x.length;n++){const r=x[n],o=r.read_number,s=r.categories,a=r.categories[0],l=[];if(s.length>1){for(let t=1;t<s.length;t++)l.push(s[t]);s.length-1>j&&(j=s.length-1)}if(a.includes("alt"))for(let n=0;n<t.variant.length;n++)a=="alt"+n.toString()&&C[i.type_supportalt+n.toString()]&&(e[o].tempscore=["alt"+n.toString()],C[i.type_supportalt+n.toString()].templates.push(e[o]));else"ref"==a?C[i.type_supportref]&&(e[o].tempscore=["ref"],C[i.type_supportref].templates.push(e[o])):"none"==a?C[i.type_supportno]&&(e[o].tempscore=l,C[i.type_supportno].templates.push(e[o])):"amb"==a?C[i.type_supportamb]&&(e[o].tempscore=l,C[i.type_supportamb].templates.push(e[o])):console.log("Unaccounted group, please check")}const O=[];for(const e in C){const r=C[e];if(0!=r.templates.length){if(e.includes(i.type_supportalt))for(let n=0;n<t.variant.length;n++)e==i.type_supportalt+n.toString()&&(1==t.variant.length?1==r.templates.length?r.messages.push({isheader:!0,t:r.templates.length+" read supporting the alternative allele"}):r.messages.push({isheader:!0,t:r.templates.length+" reads supporting the alternative allele"}):1==r.templates.length?r.messages.push({isheader:!0,t:r.templates.length+" read support the alternative allele with "+f[n]+" sequence"}):r.messages.push({isheader:!0,t:r.templates.length+" reads support the alternative allele with "+f[n]+" sequence"}));else e==i.type_supportamb?1==r.templates.length?r.messages.push({isheader:!0,t:r.templates.length+" ambiguous read"}):r.messages.push({isheader:!0,t:r.templates.length+" ambiguous reads"}):e==i.type_supportref?1==r.templates.length?r.messages.push({isheader:!0,t:r.templates.length+" read supporting the reference allele"}):r.messages.push({isheader:!0,t:r.templates.length+" reads supporting the reference allele"}):e==i.type_supportno?1==r.templates.length?r.messages.push({isheader:!0,t:r.templates.length+" read supporting neither reference nor alternative alleles"}):r.messages.push({isheader:!0,t:r.templates.length+" reads supporting neither reference nor alternative alleles"}):console.log("Unaccounted group, please check");r.widths=n,O.push(r)}}const E=[];for(let t=0;t<O.length;t++)O[t].type.includes("support_alt")&&E.push(O[t]);for(let t=0;t<O.length;t++)"support_ref"==O[t].type&&E.push(O[t]);for(let t=0;t<O.length;t++)"support_no"==O[t].type&&E.push(O[t]);for(let t=0;t<O.length;t++)"support_amb"==O[t].type&&E.push(O[t]);return{groups:E,refalleleerror:a,ref_positions:d,refalleles:u,altalleles:f,max_diff_score:j,min_diff_score:0,strand_probability:M,strand_significance:T,refseqs:h,altseqs:p,leftflankseqs:l,rightflankseqs:c,alternate_forward_count:q,alternate_reverse_count:N,reference_forward_count:S,reference_reverse_count:A}}},1270:(t,e,n)=>{const r=n(9699),o=n(3856),i=n(6718).createCanvas,s=n(2273).basecolor;t.exports=async(t,e)=>{try{const[n,a,l]=r.fileurl(t);if(n)throw n;let c=t.query.usegrade;const u=Number(t.query.allheight),f=Number(t.query.fineheight),d=Number(t.query.fineymax),h=Number(t.query.midpad),p=Number(t.query.regionspace),m=Number(t.query.width);if(!Number.isInteger(u))throw"allheight is not integer";if(!Number.isInteger(f))throw"fineheight is not integer";if(!Number.isInteger(d))throw"fineymax is not integer";if(!Number.isInteger(h))throw"midpad is not integer";if(!Number.isInteger(p))throw"regionspace is not integer";if(!Number.isFinite(m))throw"width is not a number";const g="string"==typeof t.query.rglst?JSON.parse(t.query.rglst):t.query.rglst;if(!g)throw"no rglst[]";if(!Array.isArray(g))throw"rglst is not an array";if(0==g.length)throw"empty rglst";for(const t of g)t.reverse?t.scale=e=>Math.ceil(t.width*(t.stop-e)/(t.stop-t.start)):t.scale=e=>Math.ceil(t.width*(e-t.start)/(t.stop-t.start));let y;l&&(y=await o.cache_index(a,t.query.indexURL));for(const t of g){t.items=[];let e=0;await 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r)a.push({nt:t,v:r[t]}),i+=r[t];w.fillStyle=q;const l=S*(k-i);if(w.fillRect(N+o,l,e,S*i),a.length>1){a.sort(((t,e)=>e.v-t.v));for(let t=1;t<a.length;t++){let n=0;for(let e=0;e<t;e++)n+=a[e].v;w.fillStyle=s[a[t].nt],w.fillRect(N+o,l+S*n,e,S*a[t].v)}}w.fillStyle=q;const f=u+h+A*(d-Math.min(i,d));if(w.fillRect(N+o,f,e,A*Math.min(i,d)),a.length>1)for(let t=1;t<a.length;t++){let n=0;for(let e=0;e<t;e++)n+=a[e].v;w.fillStyle=s[a[t].nt],w.fillRect(N+o,f+A*(d-Math.min(d,i-n)),e,A*Math.min(d,a[t].v))}}N+=t.width+p}e.send({src:b.toDataURL(),allgrades:x,usegrade:c,allmax:k})}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message||t})}}},2388:(t,e,n)=>{const r=n(9699),o=n(1017),i=(n(7147),n(3856)),s=n(6718).createCanvas,a=n(334);async function l(t,e,n){const o={rglst:[]};let a=0,l=0;if(t.autoscale){for(const r of t.rglst){const o=(n?r.chr.replace("chr",""):r.chr)+":"+r.start+"-"+r.stop;await i.get_lines_bigfile({args:[t.file,o],dir:e,callback:t=>{const[e,n,r,o]=t.split("\t");for(const t of o.split(",")){const e=Number(t);a=Math.min(a,e),l=Math.max(l,e)}}})}o.minv=a,o.maxv=l}else a=t.minv,l=t.maxv;const c=r.makeyscale().height(t.barheight).min(a).max(l);for(const r of t.rglst){const u={chr:r.chr,start:r.start,stop:r.stop,width:r.width,reverse:r.reverse,xoff:r.xoff},f=s(r.width,t.barheight),d=f.getContext("2d"),h=(n?r.chr.replace("chr",""):r.chr)+":"+r.start+"-"+r.stop;await i.get_lines_bigfile({args:[t.file,h],dir:e,callback:e=>{const[n,o,i,s]=e.split("\t"),u=Math.max(Number.parseInt(o),r.start),f=Math.min(Number.parseInt(i),r.stop),h=(r.reverse?r.stop-f:u-r.start)*r.width/(r.stop-r.start),p=(r.reverse?r.stop-u:f-r.start)*r.width/(r.stop-r.start);for(const e of s.split(",")){const n=Number(e);d.fillStyle=n>0?t.pcolor:t.ncolor;const r=c(n),o=Math.max(1,p-h);d.fillRect(h,r.y,o,2),n>l?(d.fillStyle=req.query.pcolor2,d.fillRect(h,0,o,2)):n<a&&(d.fillStyle=req.query.ncolor2,d.fillRect(h,t.barheight-2,o,2))}}}),u.img=f.toDataURL(),o.rglst.push(u)}return o}t.exports=t=>async(e,n)=>{try{const r=e.query,s=t[r.genome];if(!s)throw"unknown genome";let c=null;if(r.file)r.file=o.join(a.tpmasterdir,r.file);else{if(!r.url)throw"file or url missing";c=await i.cache_index(r.url,r.indexURL)}const u=await i.tabix_is_nochr(r.file||r.url,c,s),f=await l(r,c,u);n.send(f)}catch(t){t.stack&&console.log(t.stack),n.send({error:t.message||t})}}},8145:(t,e,n)=>{const r=n(9699),o=(n(1017),n(7147),n(3856)),i=n(6718).createCanvas,s=n(2273).nt2aa,a=n(2818).X,l=400,c="rgba(122,103,44,.7)",u="#edad0c",f="rgba(255,0,0,.5)",d="#ccc";function h(t,e,n,r,o){if(!t)return;if(!o.name&&!o.isoform)return;const i=[];o.name&&i.push(o.name),o.isoform&&i.push(o.isoform),t.push({chr:o.chr,start:o.start,stop:o.stop,x1:e,x2:n,y:r,isoform:o.isoform,name:i.join(" ")})}function p(t,e,n,r,o,i){const s=i/2,a=i/2,l=Math.max(i/2,6);if(o-2*s<a)return;const c=Math.ceil((o-2*s)/(a+l));if(c<=0)return;const u="+"==e;let f=Math.ceil(n+(o-a*c-l*(c-1))/2);for(let e=0;e<c;e++)t.beginPath(),u?(t.moveTo(f,r),t.lineTo(f+a,r+i/2),t.moveTo(f+a,r+i/2+1),t.lineTo(f,r+i)):(t.moveTo(f+a,r),t.lineTo(f,r+i/2),t.moveTo(f,r+i/2+1),t.lineTo(f+a,r+i)),t.stroke(),f+=a+l}t.exports=t=>async(e,n)=>{try{n.send(await async function(t,e){const[n,m,g]=r.fileurl(t);if(n)throw n;let y,v,b,_,w;if(t.query.fileIsBigbed=await o.testIfFileIsBigbed(m),t.query.getdata)t.query.getBED;else{if(y=Number(t.query.stackheight),v=Number(t.query.stackspace),b=Number(t.query.regionspace),_=Number(t.query.width),Number.isNaN(y))throw"stackheight is not integer";if(w=Math.max(10,y-2),Number.isNaN(v))throw"stackspace is not integer";if(Number.isNaN(b))throw"regionspace is not integer";if(Number.isNaN(_))throw"width is not a number"}if(t.query.usevalue){if(!t.query.usevalue.key)throw".key missing from .usevalue";if(t.query.usevalue.dropBelowCutoff&&(t.query.usevalue.dropBelowCutoff=Number(t.query.usevalue.dropBelowCutoff),Number.isNaN(t.query.usevalue.dropBelowCutoff)))throw".usevalue.dropBelowCutoff is not number"}if(t.query.bplengthUpperLimit&&(t.query.bplengthUpperLimit=Number(t.query.bplengthUpperLimit),Number.isNaN(t.query.bplengthUpperLimit)))throw"bplengthUpperLimit not number";if(!t.query.rglst)throw"no rglst[]";if(!Array.isArray(t.query.rglst))throw"rglst is not an array";if(0==t.query.rglst.length)throw"empty rglst";for(const e of t.query.rglst)e.reverse?e.scale=t=>Math.ceil(e.width*(e.stop-t)/(e.stop-e.start)):e.scale=t=>Math.ceil(e.width*(t-e.start)/(e.stop-e.start));const x=t.query.color||"#3D7A4B",k=t.query.gmregion||null,q=t.query.isoform,N=t.query.onerow,S=t.query.categories||null,A=t.query.__isgene;let M;!t.query.fileIsBigbed&&g&&(M=await o.cache_index(m,t.query.indexURL));const T=await async function(t,e,n,r,i){let s;if(r){const l=[];if(t.fileIsBigbed){const n=await o.query_bigbed_by_coord(e,r.chr,r.start,r.stop);for(const e of n){const n=e.split("\t"),r=a(n);r.chr=n[0],r.start=Number(n[1]),r.stop=Number(n[2]),r.rglst=[];for(let e=0;e<t.rglst.length;e++){const n=t.rglst[e];Math.max(r.start,n.start)<Math.min(r.stop,n.stop)&&r.rglst.push({idx:e})}0!=r.rglst.length&&l.push(r)}}else await o.get_lines_bigfile({args:[e,r.chr+":"+r.start+"-"+r.stop],dir:n,callback:e=>{const n=e.split("\t");let r={};if(t.getBED)r.rest=n.slice(3);else if(n[3])try{r=JSON.parse(n[3])}catch(t){return void(s=e)}if(!r.isoformonly||r.isoformonly==i){r.chr=n[0],r.start=Number(n[1]),r.stop=Number(n[2]),r.rglst=[];for(let e=0;e<t.rglst.length;e++){const n=t.rglst[e];Math.max(r.start,n.start)<Math.min(r.stop,n.stop)&&r.rglst.push({idx:e})}0!=r.rglst.length&&l.push(r)}}});if(s)throw"Line with invalid JSON: "+s;return[l]}const l=[];for(const[r,i]of t.rglst.entries()){const c=[];if(t.fileIsBigbed){const t=await o.query_bigbed_by_coord(e,i.chr,i.start,i.stop);for(const e of t){const t=e.split("\t"),n=a(t);n.chr=t[0],n.start=Number(t[1]),n.stop=Number(t[2]),n.rglst=[{idx:r}],c.push(n)}}else await o.get_lines_bigfile({args:[e,i.chr+":"+i.start+"-"+i.stop],dir:n,callback:e=>{const n=e.split("\t");let o={};if(t.getBED)o.rest=n.slice(3);else if(n[3])try{o=JSON.parse(n[3])}catch(t){return void(s=e)}o.chr=n[0],o.start=Number(n[1]),o.stop=Number(n[2]),o.rglst=[{idx:r}],c.push(o)}});l.push(c)}if(s)throw"Line with invalid JSON: "+s;return l}(t.query,m,M,k,q);let C;t.query.filterByName&&(C=new Set(t.query.filterByName.split(/[\s\n]/).map((t=>t.trim()))));const j=[];for(const e of T)for(const n of e){if(t.query.usevalue){const e=n[t.query.usevalue.key];if(!Number.isFinite(e))continue;if(t.query.usevalue.dropBelowCutoff&&e<t.query.usevalue.dropBelowCutoff)continue}if(!(t.query.bplengthUpperLimit&&n.stop-n.start>t.query.bplengthUpperLimit)){if(C)if(n.isoform){if(!C.has(n.isoform))continue}else{if(!n.name)continue;if(!C.has(n.name))continue}j.push(n)}}if(t.query.getdata)return{items:j};if(0==j.length){const e=i(_*t.query.devicePixelRatio,y*t.query.devicePixelRatio),n=e.getContext("2d");return t.query.devicePixelRatio>1&&n.scale(t.query.devicePixelRatio,t.query.devicePixelRatio),n.font=y+"px Arial",n.fillStyle="#aaa",n.textAlign="center",n.textBaseline="middle",n.fillText("No data in view range",_/2,y/2),{src:e.toDataURL(),height:y}}const O=Math.ceil(y/4)-1;if(N||j.length>=600){const e=j.length<200,n=i(_*t.query.devicePixelRatio,y*t.query.devicePixelRatio),r=n.getContext("2d");t.query.devicePixelRatio>1&&r.scale(t.query.devicePixelRatio,t.query.devicePixelRatio);const o=j.length<=200?[]:null;for(const n of j){const i=S&&n.category&&S[n.category]?S[n.category].color:n.color||x;r.fillStyle=i;for(const i of n.rglst){let s=0;for(let e=0;e<i.idx;e++)s+=t.query.rglst[e].width+b;const a=t.query.rglst[i.idx],l=[];n.utr5&&l.push(...n.utr5),n.utr3&&l.push(...n.utr3),!n.exon||n.coding&&0!=n.coding.length||l.push(...n.exon);for(const t of l){const e=Math.max(a.start,t[0]),i=Math.min(a.stop,t[1]),l=s+a.scale(a.reverse?i:e),c=s+a.scale(a.reverse?e:i);r.fillRect(l,O,Math.max(1,c-l),y-2*O),h(o,l,c,1,n)}const c=[];n.exon?n.coding&&n.coding.length>0&&c.push(...n.coding):c.push([n.start,n.stop]);for(const t of c){const i=Math.max(a.start,t[0]),l=Math.min(a.stop,t[1]),c=s+a.scale(a.reverse?l:i),u=s+a.scale(a.reverse?i:l);r.fillRect(c,0,Math.max(1,u-c),y),h(o,c,u,1,n),n.strand&&e&&(r.strokeStyle="white",p(r,n.strand,c,O,u-c,y-2*O))}}}return{src:n.toDataURL(),height:y,mapisoform:o}}if(t.query.hideItemNames)for(const t of j)delete t.name;let E=null;if(A&&j.length<50){E=[];for(const t of j){const e={};for(const n in t)"canvas"!=n&&"rglst"!=n&&(e[n]=t[n]);E.push(e)}}const R=t.query.rglst.reduce(((t,e)=>t+e.stop-e.start),0),I=t.query.translatecoding&&R<3*_;let P;if(I){if(!t.query.genome)throw"genome missing for translating genes";if(P=e[t.query.genome],!P)throw"invalid genome"}const F=[],L=i(10,10);let D=L.getContext("2d");t.query.devicePixelRatio>1&&D.scale(t.query.devicePixelRatio,t.query.devicePixelRatio);D.font="bold "+w+"px Arial";const B=j.length<l,z=j.length<l?[]:null;let Z=!1;k&&(Z=k.reverse);for(const e of t.query.rglst)e.reverse&&(Z=!0);j.sort(((t,e)=>Z?t.stop==e.stop?t.start-e.start:e.stop-t.stop:t.start==e.start?e.stop-t.stop:t.start-e.start));const $=j.some((t=>t.exon)),G=[0];let U=1,J=null;for(const e of j){let n=null,r=null;for(const o of e.rglst){let i=0;for(let e=0;e<o.idx;e++)i+=t.query.rglst[e].width+b;const s=t.query.rglst[o.idx],a=Math.max(e.start,s.start),l=Math.min(e.stop,s.stop);if(a<l){const t=i+s.scale(s.reverse?l:a),e=i+s.scale(s.reverse?a:l);null==n?(n=t,r=e):(n=Math.min(n,t),r=Math.max(r,e))}}if(null==n)continue;e.canvas={start:n,stop:r,stranded:null!=e.strand},e.coding&&I&&(e.willtranslate=!0,F.push(e));let o=n,i=r;if(B){const t=e.name;if(t){e.canvas.namestr=t;const n=D.measureText(t).width;e.canvas.namewidth=n,$?e.canvas.start>=n+1?(e.canvas.namestart=e.canvas.start-1,o=e.canvas.namestart-n,e.canvas.textalign="right"):e.canvas.stop+n+1<=_?(e.canvas.namestart=e.canvas.stop+1,i=e.canvas.namestart+n,e.canvas.textalign="left"):n>e.canvas.stop-e.canvas.start?e.canvas.start>_-e.canvas.stop?(e.canvas.namestart=e.canvas.start-1,o=e.canvas.namestart-n,e.canvas.textalign="right"):(e.canvas.namestart=e.canvas.stop+1,i=e.canvas.namestart+n,e.canvas.textalign="left"):(e.canvas.namehover=!0,e.canvas.textalign="left"):Math.min(_,e.canvas.stop)-Math.max(0,e.canvas.start)>=n+20?e.canvas.namein=!0:e.canvas.start>=n+1?(e.canvas.namestart=e.canvas.start-1,o=e.canvas.namestart-n,e.canvas.textalign="right"):e.canvas.stop+n+1<=_?(e.canvas.namestart=e.canvas.stop+1,i=e.canvas.namestart+n,e.canvas.textalign="left"):e.canvas.namein=!0}}e.canvas.stop-e.canvas.start>.3*_&&(J=[]);for(let t=1;t<=U;t++)if(null==G[t]||G[t]<o){e.canvas.stack=t,G[t]=i;break}null==e.canvas.stack&&(U++,G[U]=i,e.canvas.stack=U),h(z,o,i,e.canvas.stack,e)}L.width=_*t.query.devicePixelRatio;const W=(y+v)*U-v;L.height=W*t.query.devicePixelRatio,D=L.getContext("2d"),t.query.devicePixelRatio>1&&D.scale(t.query.devicePixelRatio,t.query.devicePixelRatio);D.font="bold "+w+"px Arial",D.textBaseline="middle",D.lineWidth=1;for(const e of j){const n=e.canvas;if(!n)continue;const r=S&&e.category&&S[e.category]?S[e.category].color:e.color||x,o=(y+v)*(n.stack-1);D.fillStyle=r,(e.exon||e.rglst.length>1)&&(D.strokeStyle=r,D.beginPath(),D.moveTo(n.start,Math.floor(o+y/2)+.5),D.lineTo(n.stop,Math.floor(o+y/2)+.5),D.stroke());for(const i of e.rglst){let s=0;for(let e=0;e<i.idx;e++)s+=t.query.rglst[e].width+b;const a=t.query.rglst[i.idx],l=[];e.utr3&&l.push(...e.utr3),e.utr5&&l.push(...e.utr5),!e.exon||e.coding&&0!=e.coding.length||l.push(...e.exon);for(const t of l){const n=Math.max(t[0],a.start),i=Math.min(t[1],a.stop);if(n<i){if(e.exon2color)for(const t of e.exon2color)if(n>=t.start&&i<=t.stop){D.fillStyle=t.color;break}const t=s+a.scale(a.reverse?i:n),l=s+a.scale(a.reverse?n:i);D.fillRect(t,o+O,Math.max(1,l-t),y-2*O),e.exon2color&&(D.fillStyle=r)}}const c=[];e.exon?e.coding&&e.coding.length>0&&c.push(...e.coding):c.push([e.start,e.stop]);let u=e.strand;n.stranded&&a.reverse&&(u="+"==e.strand?"-":"+");for(const t of c){const i=Math.max(t[0],a.start),l=Math.min(t[1],a.stop);if(i<l){if(e.exon2color)for(const t of e.exon2color)if(i>=t.start&&l<=t.stop){D.fillStyle=t.color;break}const t=s+a.scale(a.reverse?l:i),c=s+a.scale(a.reverse?i:l);if(D.fillRect(t,o,Math.max(1,c-t),y),e.exon2color&&(D.fillStyle=r),n.stranded&&!e.willtranslate)if(D.strokeStyle="white",n.namein){const e=(c-t-n.namewidth)/2;p(D,u,t,o+O,e,y-2*O),p(D,u,t+e+n.namewidth,o+O,e,y-2*O)}else p(D,u,t,o+O,c-t,y-2*O)}}if(n.stranded&&e.intron){D.strokeStyle=r;for(const t of e.intron){const 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t.junctionAposlst)if(e==o&&r==i){const t=JSON.parse(n[5]);t.start=o,t.stop=i,a.push(t);break}}}),!r)throw"jB not found";if(0==a.length)throw"none of jA is found";const u=l(r,t,e,n);if(0==u.length)throw"no sample passing filters for junctionB";const f=new Set;u.forEach((t=>f.add(t.i)));const d=[];for(const e of a){const n=[];for(const r of e.samples)f.has(r.i)&&(t.readcountCutoff&&r.readcount<t.readcountCutoff||n.push(r));d.push({start:e.start,stop:e.stop,v:Math.floor(c(n,.5))})}return{lst:d}}(t,e,n);const r={};if(t.iscustom&&t.getsamples){const t=await o.get_header_tabix(a(n),n.dir);if(t[0]){const e=t[0].split("\t");e.length>5&&(r.sample2client=e.slice(5))}}if(!t.rglst)throw"rglst missing";if(n.viewrangeupperlimit){if(t.rglst.reduce(((t,e)=>t+e.stop-e.start),0)>=n.viewrangeupperlimit)throw"zoom in under "+common.bplen(n.viewrangeupperlimit)+" to view details"}let i=0,u=0;const f=[],d=new Set,h=new Set;for(const r of t.rglst)await 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t.selectCohort.term.id)throw"termdb.selectCohort.term.id is not string";if("categorical"!=t.selectCohort.term.type)throw'type is not hardcoded "categorical" from termdb.selectCohort.term';if(!t.selectCohort.values)throw"values[] missing from termdb.selectCohort";if(!Array.isArray(t.selectCohort.values))throw"termdb.selectCohort.values is not array";if(0==t.selectCohort.values.length)throw"termdb.selectCohort.values[] cannot be empty";for(const e of t.selectCohort.values){if(!e.keys)throw"keys[] missing from one of selectCohort.values[]";if(!Array.isArray(e.keys))throw"keys[] is not array from one of selectCohort.values[]";if(0==e.keys.length)throw"keys[] is empty from one of selectCohort.values[]"}}if(t.restrictAncestries){if(!Array.isArray(t.restrictAncestries)||0==t.restrictAncestries.length)throw"termdb.restrictAncestries[] is not non-empty array";for(const e of t.restrictAncestries){if(!e.name)throw"name missing from one of restrictAncestries";if("object"!=typeof e.tvs)throw".tvs{} 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n}}(t);const{mayGetGeneVariantData:f,getTermTypes:d,mayGetMatchingGeneNames:p}=n(7833);t.mayGetGeneVariantData=f,t.getTermTypes=d,t.mayGetMatchingGeneNames=p,null!==(c=t.cohort)&&void 0!==c&&null!==(u=c.db)&&void 0!==u&&u.refresh&&e&&l(t,e,s)}async function f(t,e){if(!t.track)throw"no mds2 track; missing ds.track{}";const n=t.track;n.name||(n.name=t.label),function(t){if(!t.populations)return;if(!Array.isArray(t.populations))throw"populations should be array";for(const e of t.populations){if(!e.key)throw"key missing from a population";if(e.label||(e.label=e.key),!Array.isArray(e.sets))throw".sets is not an array in population: "+e.key;for(const t of e.sets){if(!t.infokey_AC)throw"infokey_AC missing from a set of population: "+e.key;if(!t.infokey_AN)throw"infokey_AN missing from a set of population: "+e.key;if(e.termfilter&&!t.termfilter_value)throw"termfilter_value missing from a set of population where termfilter is set: "+e.key}}}(n),await async function(t,e,n){if(!t)return;if(!t.chr2bcffile)throw"vcftk.chr2bcffile is missing";{if("object"!=typeof t.chr2bcffile)throw"chr2bcffile not an object";for(const e in t.chr2bcffile)t.chr2bcffile[e]=r.join(a.tpmasterdir,t.chr2bcffile[e]);const n={file:t.chr2bcffile[e.defaultcoord.chr]};if(!n.file)throw"default chr missing from chr2bcffile";await o.init_one_vcf(n,e,!0),t.info=n.info,t.format=n.format,t.samples=n.samples,t.nochr=n.nochr}if(t.AD&&t.AD.chr2bcffile){if("object"!=typeof t.AD.chr2bcffile)throw"AD.chr2bcffile not an object";for(const e in t.AD.chr2bcffile)t.AD.chr2bcffile[e]=r.join(a.tpmasterdir,t.AD.chr2bcffile[e]);const i={file:t.AD.chr2bcffile[e.defaultcoord.chr]};if(!i.file)throw"default chr missing from AD.chr2bcffile";await o.init_one_vcf(i,e,!0),t.AD.info=i.info,t.AD.format=i.format,t.AD.samples=i.samples,t.AD.nochr=i.nochr,console.log(n.label+" vcf: AD: "+t.AD.samples.length+" samples");for(const e of t.AD.samples){const t=Number(e.name);if(!Number.isInteger(t))throw"non-integer vcf sample: "+e.name;e.name=t}}if(t.samples){for(const e of t.samples){const t=Number(e.name);if(!Number.isInteger(t))throw"non-integer vcf sample: "+e.name;e.name=t}console.log(n.label+" vcf: "+t.samples.length+" samples")}else console.log(n.label+" vcf: no samples");if(t.numerical_axis&&t.numerical_axis.info_keys){if(!Array.isArray(t.numerical_axis.info_keys))throw"numerical_axis.info_keys should be an array";for(const e of t.numerical_axis.info_keys){const n=t.info[e.key];if(!n)throw'INFO field "'+e.key+'" not found for numerical_axis';if("Float"!=n.Type&&"Integer"!=n.Type)throw'INFO field "'+e.key+'" from numerical_axis not of integer or float type';if("1"!=n.Number&&"A"!=n.Number)throw'for numerical axis, INFO field "'+e.key+'" only allows to be Number=1 or Number=A'}}if(t.plot_mafcov){if(!t.AD)throw".plot_mafcov enabled but .AD{} missing from vcf";if(!t.AD.samples)throw".plot_mafcov enabled but no samples from vcf";if(!t.AD.format)throw".plot_mafcov enabled but no FORMAT fields from vcf";if(!t.AD.format.AD)throw".plot_mafcov enabled but the AD FORMAT field is missing";if("R"!=t.AD.format.AD.Number)throw"AD FORMAT field Number=R is not true";if("Integer"!=t.AD.format.AD.Type)throw"AD FORMAT field Type=Integer is not true";if(t.plot_mafcov.overlay_term){if(!n.cohort)throw"ds.cohort missing when plot_mafcov.overlay_term defined";if(!n.cohort.termdb)throw"ds.cohort.termdb missing when plot_mafcov.overlay_term defined";if(!n.cohort.termdb.q)throw"ERR: termdb.q{} missing while trying to access termdb helper functions";if(!n.cohort.termdb.q.termjsonByOneid)throw"ERR: q.termjsonByOneid missing";const e=n.cohort.termdb.q.termjsonByOneid(t.plot_mafcov.overlay_term);if(!e)throw'unknown term id "'+t.plot_mafcov.overlay_term+'" from vcftk.plot_mafcov.overlay_term';t.plot_mafcov.overlay_term=e}}if(t.termdb_bygenotype){if(!t.samples)throw".termdb_bygenotype enabled but no samples from vcf";if(!t.format)throw".termdb_bygenotype enabled but no FORMAT fields from vcf";if(!t.format.GT)throw".termdb_bygenotype enabled but the GT FORMAT field is missing";if(!n.cohort)throw"termdb_bygenotype but ds.cohort missing";if(!n.cohort.termdb)throw"termdb_bygenotype but ds.cohort.termdb missing";if(t.termdb_bygenotype.getAF){if(!t.termdb_bygenotype.termid_sex)throw"termid_sex missing for getAF at termdb_bygenotype";if(!t.termdb_bygenotype.value_male)throw"value_male missing for getAF at termdb_bygenotype";const e=n.cohort.termdb.q.getSample2value(t.termdb_bygenotype.termid_sex);t.termdb_bygenotype.male_samples=new Set;for(const n of e)n.value==t.termdb_bygenotype.value_male&&t.termdb_bygenotype.male_samples.add(n.sample);if(!t.termdb_bygenotype.sex_chrs)throw"sex_chrs missing for getAF at termdb_bygenotype";if(!Array.isArray(t.termdb_bygenotype.sex_chrs))throw"sex_chrs is not array";t.termdb_bygenotype.sex_chrs=new Set(t.termdb_bygenotype.sex_chrs)}}if(t.samples){t.sample2arrayidx=new Map;for(const[e,n]of t.samples.entries())t.sample2arrayidx.set(n.name,e)}}(n.vcf,e,t),function(t){if(!t.info_fields)return;if(!Array.isArray(t.info_fields))throw"tk.info_fields is not array";for(const e of t.info_fields){if(!e.key)throw".key missing from one of tk.info_fields[]";if(t.vcf&&t.vcf.info&&!t.vcf.info[e.key])throw`info field ${e.key} missing from tk.vcf.info{}`;if(e.label||(e.label=e.key),e.iscategorical){if(!Array.isArray(e.values))throw".values[] not an array of categorical INFO field: "+e.key;for(const t of e.values){if(!t.key)throw"key missing from a value of categorical INFO: "+e.key;t.label||(t.label=t.key)}}else if(e.isfloat||e.isinteger){if(!e.range)throw".range{} missing from a numerical INFO: "+e.key;s(e.range,"tk.info_fields[]")}else if(!e.isflag)throw"tk.info_fields unknown type: "+e.key}}(n),await async function(t,e,n){if(!t)return;if(!Array.isArray(t.tracks))throw"ld.tracks[] not an 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e.term.groupsetting.lst[e.q.groupsetting.predefined_groupset_idx]){if(!Array.isArray(n.values))throw"group.values[] not array from tw.term.groupsetting.lst[]";if(-1!=n.values.findIndex((e=>e.key==t)))return n.name}}(t[n.term.id],n);e&&(t[n.term.id]=e)}}function S(t,e){for(const n of t)if(n.startunbounded){if(e<n.stop)return n.label;if(n.stopinclusive&&e==n.stop)return n.label}else if(n.stopunbounded){if(e>n.start)return n.label;if(n.startinclusive&&e==n.start)return n.label}else if((e>n.start||e===n.start&&n.startinclusive)&&(e<n.stop||e===n.stop&&n.stopinclusive))return n.label}function A(t){for(const n of t)if(null==n.id||""==n.id){var e;if(null==n||null===(e=n.term)||void 0===e||!e.id)throw"tw.id and tw.term are both missing";n.id=n.term.id}else n.term||(n.term={id:n.id})}async function M(t,e,n,o){if(A(e),o){if(!Array.isArray(o))throw"geneTwLst not array";t.isoforms=[];for(const e of o){var a;if(null==e||null===(a=e.term)||void 0===a||!a.name)throw"gene tw missing .term.name";if(e.term.isoform)t.isoforms.push(e.term.isoform);else{var c,f;if("object"!=typeof t.genome)throw"serverside genome obj missing, needed to map gene name to canonical isoform";if(null===(c=t.genome)||void 0===c||null===(f=c.genedb)||void 0===f||!f.get_gene2canonicalisoform)throw"gene2canonicalisoform not supported on this genome";const n=t.genome.genedb.get_gene2canonicalisoform.get(e.term.name);if(null==n||!n.isoform)continue;t.isoforms.push(n.isoform)}}}"samples"==t.get&&((t.ssm_id_lst||t.isoform)&&(e.some((t=>"ssm.ssm_id"==t.id))||e.push({term:{id:"ssm.ssm_id"}}),e.some((t=>"case.observation.read_depth.t_alt_count"==t.id))||e.push({term:{id:"case.observation.read_depth.t_alt_count"}}),e.some((t=>"case.observation.read_depth.t_depth"==t.id))||e.push({term:{id:"case.observation.read_depth.t_depth"}}),e.some((t=>"case.observation.read_depth.n_depth"==t.id))||e.push({term:{id:"case.observation.read_depth.n_depth"}}),e.some((t=>"case.observation.sample.tumor_sample_uuid"==t.id))||e.push({term:{id:"case.observation.sample.tumor_sample_uuid"}})),o&&(e.some((t=>"case.submitter_id"==t.id))||e.push({term:{id:"case.submitter_id"}})),e.some((t=>"case.case_id"==t.id))||e.push({term:{id:"case.case_id"}})),"summary"!=t.get&&"sunburst"!=t.get||e.some((t=>"case.submitter_id"==t.id))||e.push({term:{id:"case.submitter_id"}});const d=[];for(const t of e){const e=n.cohort.termdb.q.termjsonByOneid(t.term.id);e&&d.push({term:e,q:t.q})}const h=e.map((t=>t.term.id));t.hiddenmclass&&(h.push("ssm.consequence.transcript.consequence_type"),h.push("ssm.consequence.transcript.transcript_id")),t.rglst&&(h.push("ssm.chromosome"),h.push("ssm.start_position"));const p={size:1e4,fields:h.join(",")};v(t,n),p.filters=z.filters(t,n);const m=q(t),g=await i.post(s.join(u,z.endpoint),{headers:m,body:JSON.stringify(p)});let y;delete t.isoforms;try{y=JSON.parse(g.body)}catch(t){throw"invalid JSON from GDC for variant2samples query"}if(!y.data||!y.data.hits)throw"variant2samples data structure not data.hits[]";if(!Array.isArray(y.data.hits))throw"variant2samples re.data.hits is not array for query";const b=[];for(const e of y.data.hits){if(!e.case)throw"variant2samples .case{} missing from a hit";const r={};if(e.ssm&&(r.ssm_id=e.ssm.ssm_id),t.hiddenmclass){var w;if(!Array.isArray(null===(w=e.ssm)||void 0===w?void 0:w.consequence))continue;const n={};if(_(n,e.ssm.consequence.find((e=>e.transcript.transcript_id==t.isoform))),t.hiddenmclass.has(n.class))continue}if(t.rglst){var x,k;if(null===(x=e.ssm)||void 0===x||!x.chromosome||null===(k=e.ssm)||void 0===k||!k.start_position)continue;if(!t.rglst.find((t=>t.chr==e.ssm.chromosome&&t.start<e.ssm.start_position&&t.stop>=e.ssm.start_position)))continue}var M,O,E,R;if(r.sample_id=await T(e.case,n,!0),e.case.case_id)r.sample_URLid=e.case.case_id,null!==(M=e.case)&&void 0!==M&&null!==(O=M.observation)&&void 0!==O&&null!==(E=O[0])&&void 0!==E&&null!==(R=E.sample)&&void 0!==R&&R.tumor_sample_uuid&&(r.sample_URLid=r.sample_URLid+"?bioId="+e.case.observation[0].sample.tumor_sample_uuid);for(const t of d)N(r,e.case,t);C(e.case,r),j(r,n),b.push(r)}if(function(t,e){for(const o of e){var n;if(("integer"==o.term.type||"float"==o.term.type)&&null!==(n=o.q)&&void 0!==n&&n.mode)if("discrete"==o.q.mode||"binary"==o.q.mode){const e={};for(const n of t){const t=n[o.term.id];Number.isFinite(t)&&("min"in e?(e.min=Math.min(t,e.min),e.max=Math.max(t,e.max)):(e.min=t,e.max=t))}const n=(0,r.compute_bins)(o.q,(t=>e));for(const e of t){const t=e[o.term.id];Number.isFinite(t)&&(e[o.term.id]=S(n,t))}}else if("continuous"!=o.q.mode)throw"mayApplyBinning: unknown numeric q.mode"}}(b,d),o){const t={gene:o.map((t=>t.term.name)).join(","),twLst:d},e=await n.queries.geneCnv.bygene.get(t);for(const t of e)for(const e of t.samples)b.push(e)}const I=new Map;for(const t of b)l([t],I,t.ssm_id);return[...I.values()]}async function T(t,e,n){var r,o,i;return n&&t.submitter_id?t.submitter_id:null!=t&&null!==(r=t.observation)&&void 0!==r&&null!==(o=r[0])&&void 0!==o&&null!==(i=o.sample)&&void 0!==i&&i.tumor_sample_uuid?await e.aliquot2submitter.get(t.observation[0].sample.tumor_sample_uuid):t.case_id||t.submitter_id}function C(t,e){if(!t.observation)return;const n=t.observation[0];n&&n.read_depth&&(e.formatK2v={TumorAC:n.read_depth.t_depth-n.read_depth.t_alt_count+","+n.read_depth.t_alt_count,NormalDepth:n.read_depth.n_depth})}function j(t,e){var n;const r=t["case.project.project_id"];r&&(t.caseIsOpenAccess=null===(n=e.gdcOpenProjects)||void 0===n?void 0:n.has(r))}async function O(t,e,n,r){A(t);const o=[];for(const e of t)e.term&&"categorical"==e.term.type&&o.push({id:e.id,path:e.id.replace("case.","").replace(/\./g,"__"),type:e.term.type});const s=function(t){const e=[];for(const n of t)if(n.id)if(n.type="categorical")e.push(n.path+" {buckets { doc_count, key }}");else{if("integer"!=n.type&&"float"!=n.type)throw"unknown term type";e.push(n.path+" {stats { count }}")}const n=`query termislst2total( $filters: FiltersArgument) {\n\t\texplore {\n\t\t\tcases {\n\t\t\t\taggregations (filters: $filters, aggregations_filter_themselves: true) {\n\t\t\t\t\t${e.join("\n")}\n\t\t\t\t}\n\t\t\t}\n\t\t}\n\t}`;return n}(o),a=function(t,e){const n={filters:{op:"and",content:[{op:"in",content:{field:"cases.available_variation_data",value:["ssm"]}}]}};if(t&&t.tid2value)for(const r in t.tid2value){e.cohort.termdb.q.termjsonByOneid(r)&&n.filters.content.push({op:"in",content:{field:r.replace(/^case\./,"cases."),value:[t.tid2value[r]]}})}t&&t.ssm_id_lst&&n.filters.content.push({op:"=",content:{field:"cases.gene.ssm.ssm_id",value:t.ssm_id_lst.split(",")}});return n}(e,r),l=await i.post(f,{headers:q(e),body:JSON.stringify({query:s,variables:a})});let c;try{c=JSON.parse(l.body)}catch(t){throw"invalid JSON from GDC for cohortTotal for query :"+s+" and filter: "+filter}const u=["data","explore","cases","aggregations"];let d=c[u[0]];for(let t=1;t<u.length;t++)if(d=d[u[t]],!d)throw"."+u[t]+" missing from data structure of termid2totalsize2 for query :"+s+" and filter: "+filter;for(const t of o){if("categorical"==t.type&&!Array.isArray(d[t.path].buckets))throw u.join(".")+" not array for query :"+s+" and filter: "+filter;if(("integer"==t.type||"float"==t.type)&&"object"!=typeof d[t.path].stats)throw u.join(".")+" not object for query :"+s+" and filter: "+filter}const h=new Map;for(const t of o)if("categorical"==t.type){const e=d[t.path].buckets;let n=[];for(const t of e)n.push([t.key.replace(".","__"),t.doc_count]);h.set(t.id,n)}else if("integer"==t.type||"float"==t.type){const e=d[t.path].stats.count;h.set(t.id,{total:e})}return n?[h,n]:h}function E(t){const e=["consequence.transcript.transcript_id","consequence.transcript.consequence_type","consequence.transcript.aa_change"];t.queries.snvindel.m2csq.get=async t=>{const n=await i(u+"/ssms/"+t.ssm_id+"?fields="+e.join(","),{method:"GET",headers:q(t)});let r;try{r=JSON.parse(n.body)}catch(t){throw"invalid json in response"}if(!r.data||!r.data.consequence)throw"returned data not .data.consequence";if(!Array.isArray(r.data.consequence))throw".data.consequence not array";return r.data.consequence.map((t=>t.transcript))}}function R(t,e){t.queries.singleSampleMutation.get=async(n,r)=>{if(!n)throw"sampleName missing";return r.case_id=await async function(t){const e=await i.post("https://api.gdc.cancer.gov/cases",{headers:{"Content-Type":"application/json",Accept:"application/json"},body:JSON.stringify({size:1,fields:"case_id,submitter_id",filters:{op:"or",content:[{op:"=",content:{field:"samples.portions.analytes.aliquots.aliquot_id",value:[t]}},{op:"=",content:{field:"submitter_id",value:[t]}},{op:"=",content:{field:"samples.submitter_id",value:[t]}}]}})}),n=JSON.parse(e.body);for(const t of n.data.hits)if(t.case_id)return t.case_id;throw"cannot convert to case_id (uuid)"}(n),await P(r,t,e)}}function I(t){return async(e,n)=>{try{const r=t[e.query.genome];if(!r)throw"invalid genome";const o=r.datasets[e.query.dslabel];if(!o)throw"invalid dslabel";if(!e.query.case_id)throw".case_id missing";n.send({mlst:await P(e.query,o,r)})}catch(t){t.stack&&console.log(t.stack),n.send({error:t.message||t})}}}async function P(t,e,n){const r=[];{const e=await i.post(s.join(u,B.endpoint),{headers:q(t),body:JSON.stringify({size:1e3,fields:B.fields.join(","),filters:B.filters(t)})}),a=JSON.parse(e.body);for(const t of a.data.hits){let e;for(const n of t.consequence)if(n.transcript&&n.transcript.gene&&n.transcript.gene.symbol){e=n.transcript.gene.symbol;break}if(!e)continue;const i=n.genedb.get_gene2canonicalisoform.get(e);if(null==i||!i.isoform)continue;let s=t.consequence.find((t=>t.transcript.transcript_id==i.isoform));s||(s=t.consequence[0]);const a=s.transcript.aa_change||s.transcript.consequence_type,[l,c,u]=o.vepinfo(s.transcript.consequence_type);r.push({dt:o.dtsnvindel,mname:a,class:c,gene:s.transcript.gene.symbol,chr:t.chromosome,pos:t.start_position,ref:t.reference_allele,alt:t.tumor_allele})}}{const e=await async function(t){const e=q(t),n=await i.post(s.join(u,"files"),{headers:e,body:JSON.stringify({size:1e4,fields:["cases.samples.sample_type","data_type","file_id","data_format","experimental_strategy","analysis.workflow_type"].join(","),filters:function(t){if(!t.case_id)throw".case_id missing";return{op:"and",content:[{op:"in",content:{field:"cases.case_id",value:[t.case_id]}},{op:"in",content:{field:"data_type",value:["Masked Copy Number Segment","Copy Number Segment","Transcript Fusion"]}}]}}(t)})}),r=JSON.parse(n.body);if(!Array.isArray(r.data.hits))throw"re.data.hits[] not array";let a,l,c;for(const t of r.data.hits)if("BEDPE"!=t.data_format){if("TXT"==t.data_format){if("Genotyping Array"==t.experimental_strategy){var f,d,h;const e=null===(f=t.cases)||void 0===f||null===(d=f[0].samples)||void 0===d||null===(h=d[0])||void 0===h?void 0:h.sample_type;if(!e)continue;if(e.includes("Normal"))continue;if("Masked Copy Number Segment"!=t.data_type)continue;a=t.file_id;continue}if("WGS"==t.experimental_strategy){if(!t.file_id)continue;if("Copy Number Segment"!=t.data_type)continue;l=t.file_id;continue}}}else{var p;if("RNA-Seq"!=t.experimental_strategy)continue;if("Arriba"!=(null===(p=t.analysis)||void 0===p?void 0:p.workflow_type))continue;if("Transcript Fusion"!=t.data_type)continue;c=t.file_id}const m=[];if(l){const t=(await i(s.join(u,"data")+"/"+l,{method:"GET",headers:e})).body.split("\n");for(let e=1;e<t.length;e++){const n=t[e].split("\t");if(7!=n.length)continue;const r=Number(n[4]),i=Number(n[5]),s=Number(n[6]);if(Number.isNaN(r)||Number.isNaN(i)||Number.isNaN(s))continue;const a={dt:o.dtcnv,chr:n[1],start:Number(n[2]),stop:Number(n[3]),value:r};!a.chr||Number.isNaN(a.start)||Number.isNaN(a.stop)||(m.push(a),r>0&&0==s&&i>0&&m.push({dt:o.dtloh,chr:a.chr,start:a.start,stop:a.stop,segmean:.5}))}}else if(a){const t=(await i(s.join(u,"data")+"/"+a,{method:"GET",headers:e})).body.split("\n");for(let e=1;e<t.length;e++){const n=t[e].split("\t");if(6!=n.length)continue;if(!n[1])continue;const r={dt:o.dtcnv,chr:"chr"+n[1],start:Number(n[2]),stop:Number(n[3]),value:Number(n[5])};Number.isNaN(r.start)||Number.isNaN(r.stop)||Number.isNaN(r.value)||m.push(r)}}if(c)try{const t=(await i(s.join(u,"data")+"/"+c,{method:"GET",headers:e})).body.split("\n");for(let e=1;e<t.length;e++){const n=t[e].split("\t"),r={dt:o.dtfusionrna,chrA:n[0],posA:Number(n[1]),chrB:n[3],posB:Number(n[4])};r.chrA&&r.chrB&&!Number.isNaN(r.posA)&&!Number.isNaN(r.posB)&&(k(r,n[6]),m.push(r))}}catch(t){}return m}(t);r.push(...e)}return r}function F(t){return async(e,n)=>{try{if(!t[e.query.genome])throw"invalid genome";n.send({genes:await L({filter:e.query.filter0,CGConly:parseInt(e.query.CGConly),maxGenes:e.query.maxGenes})})}catch(t){t.stack&&console.log(t.stack),n.send({error:t.message||t})}}}async function L({filter:t,CGConly:e,maxGenes:n}){let r={op:"and",content:[]};if(t){if("object"!=typeof t)throw"filter not 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B={endpoint:"/ssms",size:1e5,fields:["ssm_id","chromosome","start_position","reference_allele","tumor_allele","consequence.transcript.transcript_id","consequence.transcript.consequence_type","consequence.transcript.aa_change","consequence.transcript.gene.symbol"],filters:t=>{const e={op:"and",content:[]};if(t.isoform){if("string"!=typeof t.isoform)throw".isoform value not string";e.content.push({op:"=",content:{field:"consequence.transcript.transcript_id",value:[t.isoform]}})}if(t.case_id){if("string"!=typeof t.case_id)throw".case_id value not string";e.content.push({op:"=",content:{field:"cases.case_id",value:[t.case_id]}})}if(t.set_id){if("string"!=typeof t.set_id)throw".set_id value not string";e.content.push({op:"in",content:{field:"cases.case_id",value:[t.set_id]}})}return t.filter0&&e.content.push(t.filter0),t.filterObj&&e.content.push(c(t.filterObj)),e}},z={endpoint:"/ssm_occurrences",size:1e5,fields:["ssm.ssm_id","case.case_id","case.submitter_id","case.observation.sample.tumor_sample_uuid"],filters:(t,e)=>{const n={op:"and",content:[]};if(t.ssm_id_lst){if("string"!=typeof t.ssm_id_lst)throw"ssm_id_lst not string";n.content.push({op:"=",content:{field:"ssm.ssm_id",value:t.ssm_id_lst.split(",")}})}else if(t.isoform)n.content.push({op:"=",content:{field:"ssms.consequence.transcript.transcript_id",value:[t.isoform]}});else{if(!t.isoforms)throw".ssm_id_lst, .isoform, .isoforms are all missing";if(!Array.isArray(t.isoforms))throw".isoforms[] not array";n.content.push({op:"in",content:{field:"ssms.consequence.transcript.transcript_id",value:t.isoforms}})}if(t.rglst&&(n.content.push({op:">=",content:{field:"ssms.start_position",value:t.rglst[0].start}}),n.content.push({op:"<=",content:{field:"ssms.start_position",value:t.rglst[0].stop}})),t.set_id){if("string"!=typeof t.set_id)throw".set_id value not string";n.content.push({op:"in",content:{field:"cases.case_id",value:[t.set_id]}})}if(t.filter0&&n.content.push(t.filter0),t.filterObj&&n.content.push(c(t.filterObj)),t.tid2value)for(const r in t.tid2value){const o=e.cohort.termdb.q.termjsonByOneid(r);if(o)if("categorical"==o.type)n.content.push({op:"in",content:{field:r,value:[t.tid2value[r]]}});else if("integer"==o.type)for(const e of t.tid2value[r])n.content.push({op:e.op,content:{field:r,value:e.range}})}return n}}},9191:(t,e,n)=>{"use strict";n.r(e),n.d(e,{client_copy:()=>J,cnvByRangeGetter_file:()=>st,init:()=>U,snvindelByRangeGetter_bcf:()=>Y,ssmIdFieldsSeparator:()=>Z,svfusionByRangeGetter_file:()=>it,validate_termdb:()=>W});var r=n(7147),o=n.n(r),i=n(4521),s=n.n(i),a=n(1017),l=n.n(a),c=n(9064),u=n(6718),f=n(5243);const d=n(6452),h=n(1017),p=n(1575).CG,m=n(334),g=process.env.PP_GDC_HOST||"https://api.gdc.cancer.gov",y=g+(g.includes("/v0")?"":"/v0")+"/graphql",v=h.join(g,"ssm_occurrences/_mapping"),b={default:{mode:"discrete",type:"regular-bin",bin_size:1,startinclusive:!1,stopinclusive:!0,first_bin:{startunbounded:!0,stop:0},last_bin:{start:1,stopunbounded:!0}}},_={"case.demographic.age_at_index":{default:{mode:"discrete",type:"regular-bin",bin_size:10,startinclusive:!1,stopinclusive:!0,first_bin:{startunbounded:!0,stop:30}}},"case.demographic.days_to_birth":{default:{mode:"discrete",type:"regular-bin",bin_size:1e4,startinclusive:!1,stopinclusive:!0,first_bin:{startunbounded:!0,stop:-3e4}}},"case.demographic.days_to_death":{default:{mode:"discrete",type:"regular-bin",bin_size:1e3,startinclusive:!1,stopinclusive:!0,first_bin:{startunbounded:!0,stop:1e3}}}},w="ssm_occurrence_centrics";async function x(t){const e=new Map,n=await d(v,{method:"GET",headers:{"Content-Type":"application/json",Accept:"application/json"}});let r;try{r=JSON.parse(n.body)}catch(t){throw"invalid JSON from GDC dictionary"}if(!r._mapping)throw"returned data does not have ._mapping";if(!Array.isArray(r.fields))throw".fields not array";if(!Array.isArray(r.nested))throw".nested not array";const o=new Set(r.nested);let i=0,s=0,a=0,l=0,c=0,u=0;for(const t of r.fields){if(N(t)){i++;continue}const n=t.split(".");for(let t=1;t<n.length;t++){const i=n.slice(0,t).join("."),u=i+"."+n[t],f=n[t][0].toUpperCase()+n[t].slice(1).replace(/_/g," "),d={id:u.toLowerCase(),name:f,included_types_set:new Set,child_types_set:new Set};if(t==n.length-1){d.isleaf=!0;const t=r._mapping[w+"."+u];t&&("keyword"==t.type?(d.type="categorical",a++):"long"==t.type?(d.type="integer",d.bins=_[d.id]||JSON.parse(JSON.stringify(b)),_[d.id]||console.log("lack bin config for integer "+d.id),l++):"double"==t.type&&(d.type="float",d.bins=_[d.id]||JSON.parse(JSON.stringify(b)),_[d.id]||console.log("lack bin config for float "+d.id),c++)),d.type||s++,k(d)}if(1==t);else if(d.parent_id=i,d.type){d.included_types_set.add(d.type);let t=e.get(i);for(;t&&(t.included_types_set.add(d.type),t.child_types_set.add(d.type),t.parent_id);)t=e.get(t.parent_id)}o.has(u)&&(d.isObjectList=!0),e.set(u,d)}}for(const t of e.values())t.type||u++,t.included_types=[...t.included_types_set],t.child_types=[...t.child_types_set],delete t.included_types_set,delete t.child_types_set;console.log("GDC dictionary:",e.size,"total variables,",i,"lines skipped,",s,"lines with unknown term type,","categorical="+a,"integer="+l,"float="+c,"parent="+u),Object.freeze(e),function(t,e){const n=t.cohort.termdb.q={};async function r(e,n){if(0==e.length||!n)return;const r=await t.termdb.termid2totalsize2.get(e.map((t=>t.id)),JSON.parse(n));for(const t of e)if(t){const e=r.get(t.id);"categorical"==t.type&&e?e.length?t.samplecount=e.map((t=>t[1])).reduce(((t,e)=>t+e)):(t.disabled=!0,t.samplecount=0):"integer"!=t.type&&"float"!=t.type||(t.samplecount=e.total,0==e.total&&(t.disabled=!0))}}n.getRootTerms=async(t,n=null)=>{const o=[];for(const t of e.values())null==t.parent_id&&o.push(JSON.parse(JSON.stringify(t)));return await r(o,n),o},n.getTermChildren=async(t,n=null,o=null)=>{const i=[];for(const n of e.values())n.parent_id==t&&i.push(JSON.parse(JSON.stringify(n)));return await r(i,o),i},n.findTermByName=async(t,n=null,o,i=null,s=null)=>{(t=t.toLowerCase()).includes(" ")&&(t=t.replace(/\s/g,"_"));const a=[];for(const n of e.values())s&&!p(n,s)||n.id.includes(t)&&a.push(JSON.parse(JSON.stringify(n)));return await r(a,i),a},n.getAncestorIDs=t=>{if(!e.has(t))return;const n=t.split("."),r=[];for(let t=1;t<n.length;t++)r.push(n.slice(0,t+1).join("."));return r},n.getAncestorNames=n.getAncestorIDs,n.termjsonByOneid=t=>{const n=e.get(t);return n?JSON.parse(JSON.stringify(n)):null},n.getSupportedChartTypes=()=>{const t={},n={};for(const r of e.values())r.type&&(r.cohort in t||(t[r.cohort]=["barchart","table","regression"],n[r.cohort]=0),"survival"!=r.type||t[r.cohort].includes("survival")||t[r.cohort].push("survival"),"condition"!=r.type||t[r.cohort].includes("cuminc")||t[r.cohort].push("cuminc"),"float"!=r.type&&"integer"!=r.type||(n[r.cohort]+=r.samplecount));for(const e in n)n[e]>0&&t[e].push("boxplot"),n[e]>1&&t[e].push("scatterplot");return t}}(t,e),t.cohort.termdb.termtypeByCohort=[],a&&t.cohort.termdb.termtypeByCohort.push({cohort:"",type:"categorical"}),l&&t.cohort.termdb.termtypeByCohort.push({cohort:"",type:"integer"}),c&&t.cohort.termdb.termtypeByCohort.push({cohort:"",type:"float"}),await async function(t){var e,n,r;const o={"Content-Type":"application/json",Accept:"application/json"},i={filters:{op:"and",content:[{op:"=",content:{field:"access",value:"open"}},{op:"=",content:{field:"data_type",value:"Masked Somatic Mutation"}}]},facets:"cases.project.project_id",size:0},s=await d(h.join(g,"files"),{method:"POST",headers:o,body:JSON.stringify(i)}),a=JSON.parse(s.body);if(t.gdcOpenProjects=new Set,null!=a&&null!==(e=a.data)&&void 0!==e&&null!==(n=e.aggregations)&&void 0!==n&&null!==(r=n["cases.project.project_id"])&&void 0!==r&&r.buckets){for(const e of a.data.aggregations["cases.project.project_id"].buckets)e.key&&t.gdcOpenProjects.add(e.key);console.log("GDC open-access projects:",t.gdcOpenProjects.size)}else console.log("getting open project_id but return is not re.data.aggregations['cases.project.project_id'].buckets")}(t),async function(){try{await S(g+"/ssms"),await S(g+"/ssm_occurrences"),await S(g+"/cases"),await S(g+"/files"),await S(g+"/analysis/top_mutated_genes_by_project"),await async function(t){const e=new Date;try{const e="query termislst2total( $filters: FiltersArgument) {\n\t\texplore {\n\t\t\tcases {\n\t\t\t\taggregations (filters: $filters, aggregations_filter_themselves: true) {\n\t\t\t\t\tprimary_site {buckets { doc_count, key }}\n\t\t\t\t}\n\t\t\t}\n\t\t}}";await d.post(t,{headers:{"Content-Type":"application/json",Accept:"application/json"},body:JSON.stringify({query:e,variables:{}})})}catch(e){throw"gdc api down: "+t}console.log("GDC GraphQL API okay: "+t,new Date-e,"ms")}(y)}catch(t){console.error(`\n##########################################\n#\n# GDC API unavailable\n# ${g}\n# ${y}\n#\n##########################################`)}}(),async function(t){try{if(t.aliquot2submitter={cache:new Map,get:async e=>t.aliquot2submitter.cache.has(e)?t.aliquot2submitter.cache.get(e):e},m.features.stopGdcCacheAliquot)return console.log("GDC aliquot2submitter not cached!");const e=await A(t,1,0);if(!Number.isInteger(e))throw"gdc totalCases not integer";const n=new Date;console.log("Start to cache aliquot IDs of",e,"cases...");const r=1e3;for(let n=0;n<Math.ceil(e/r);n++)await A(t,r,1e3*n);console.log("Done caching",t.aliquot2submitter.cache.size,"aliquot IDs.",new Date-n,"ms")}catch(t){console.log("Error at caching: "+t)}}(t)}function k(t){"case.diagnoses.age_at_diagnosis"!=t.id||(t.printDays2years=!0)}const q=new Set(["case.consent_type","case.days_to_consent","case.days_to_index"]);function N(t){return!!(t.startsWith("ssm")||t.startsWith("case.observation")||t.startsWith("case.available_variation_data"))||(!(!t.endsWith("_id")||t.endsWith("project_id"))||(!!q.has(t)||void 0))}async function S(t){try{const e=new Date;await d(t),console.log("GDC API okay: "+t,new Date-e,"ms")}catch(e){throw"gdc api down: "+t}}async function A(t,e,n,r){var o,i,s;const a=["fields=samples.portions.analytes.aliquots.aliquot_id,samples.submitter_id"];if(r)a.push('filters={"op":"and","content":[{"op":"=","content":{"field":"samples.portions.analytes.aliquots.aliquot_id","value":["'+r+'"]}}]}');else{if(!Number.isInteger(e)||!Number.isInteger(n))throw"size and from not integers";a.push("size="+e),a.push("from="+n)}const l=await d(g+"/cases?"+a.join("&")),c=JSON.parse(l.body);if(!Array.isArray(null==c||null===(o=c.data)||void 0===o?void 0:o.hits))throw"re.data.hits[] not array";for(const e of c.data.hits)if(Array.isArray(e.samples))for(const n of e.samples){const e=n.submitter_id;if(Array.isArray(n.portions))for(const r of n.portions)if(Array.isArray(r.analytes))for(const n of r.analytes)if(Array.isArray(n.aliquots))for(const r of n.aliquots){const n=r.aliquot_id;if(!n)throw"aliquot.aliquot_id missing";t.aliquot2submitter.cache.set(n,e)}}return null===(i=c.data)||void 0===i||null===(s=i.pagination)||void 0===s?void 0:s.total}var M=n(817),T=n(3856),C=n(3625),j=n(7027),O=n(334),E=n.n(O),R=n(2273),I=n(2852),P=n(394),F=n(1711),L=n(1883),D=n(2188),B=n(2974),z=n(3795);const Z=".",$="Ancestry_PC_",G="Unannotated";async function U(t,e,n,r=null,i=null){var s,a;await W(t),t.queries&&(await async function(t,e){const n=t.queries.snvindel;if(!n)return;if(n.url){if(!n.url.base)throw".snvindel.url.base missing";if(!n.url.key)throw".snvindel.url.key missing"}if(!n.byisoform&&!n.byrange)throw"byisoform and byrange are both missing on queries.snvindel";if(n.byrange)if(n.byrange.gdcapi)f.validate_query_snvindel_byrange(t);else if(n.byrange.bcffile){var r;n.byrange.bcffile=l().join(E().tpmasterdir,n.byrange.bcffile),n.byrange._tk={file:n.byrange.bcffile},n.byrange.get=await Y(t,e),null!==(r=n.byrange._tk)&&void 0!==r&&r.samples.length||delete n.byrange._tk.samples,V(t,n.byrange._tk.samples,"snvindel.byrange.bcffile")}else{if(!n.byrange.chr2bcffile)throw"unknown query method for queries.snvindel.byrange";n.byrange._tk={chr2files:{}};for(const t in n.byrange.chr2bcffile)n.byrange._tk.chr2files[t]={file:l().join(E().tpmasterdir,n.byrange.chr2bcffile[t])};delete n.byrange.chr2bcffile,n.byrange.get=await Y(t,e),n.byrange._tk.samples.length||delete n.byrange._tk.samples,V(t,n.byrange._tk.samples,"snvindel.byrange.bcffile")}if(n.byisoform){if(!n.byisoform.gdcapi)throw"unknown query method for queries.snvindel.byisoform";f.validate_query_snvindel_byisoform(t)}if(n.m2csq){if(!n.m2csq.by)throw".by missing from queries.snvindel.m2csq";if("ssm_id"!=n.m2csq.by)throw"unknown value of queries.snvindel.m2csq.by";if(!n.m2csq.gdcapi)throw"unknown query method for queries.snvindel.m2csq";f.validate_m2csq(t)}}(t,e),await async function(t,e){const n=t.queries.svfusion;if(!n)return;if(!n.byrange)throw"byrange missing from queries.svfusion";if(n.byrange){if(!n.byrange.file)throw"unknown query method for svfusion.byrange";n.byrange.file=l().join(E().tpmasterdir,n.byrange.file),n.byrange.get=await it(t,e),V(t,n.byrange.samples,"svfusion.byrange")}}(t,e),await async function(t,e){const n=t.queries.geneCnv;if(!n)return;if(!n.bygene)throw"geneCnv.bygene missing";n.bygene.gdcapi&&f.validate_query_geneCnv2(t)}(t),await async function(t,e){const n=t.queries.cnv;if(!n)return;if(!n.byrange)throw"byrange missing from queries.cnv";if(n.byrange){if(!n.byrange.file)throw"unknown query method for cnv.byrange";n.byrange.file=l().join(E().tpmasterdir,n.byrange.file),n.byrange.get=await st(t,e),V(t,n.byrange.samples,"cnv.byrange")}}(t,e),await async function(t,e){const n=t.queries.ld;if(!n)return;if(!Array.isArray(n.tracks)||!n.tracks.length)throw"ld.tracks[] not nonempty array";for(const t of n.tracks){if(!t.name)throw"name missing from one of ld.tracks[]";if(!t.file)throw".file missing from one of ld.tracks[]";t.file0=t.file,t.file=l().join(E().tpmasterdir,t.file),await T.validate_tabixfile(t.file),t.nochr=await T.tabix_is_nochr(t.file,null,e)}if(!n.overlay)throw"ld.overlay{} missing";if(!n.overlay.color_0)throw"ld.overlay.color_0 missing";if(!n.overlay.color_1)throw"ld.overlay.color_1 missing"}(t,e),await async function(t,e){const n=t.queries.geneExpression;if(!n)return;if(n.gdcapi)return void f.validate_query_geneExpression(t);if(!n.file)throw".file missing from queries.geneExpression";n.file=l().join(E().tpmasterdir,n.file),await T.validate_tabixfile(n.file),n.nochr=await T.tabix_is_nochr(n.file,null,e),n.get=async e=>{const r=await tt(e,null,t),o=new Map;for(const t of e.genes)o.set(t.gene,{}),await T.get_lines_bigfile({args:[n.file,(n.nochr?t.chr.replace("chr",""):t.chr)+":"+t.start+"-"+t.stop],dir:n.dir,callback:e=>{const n=e.split("\t");let i;try{i=JSON.parse(n[3])}catch(t){return}i.gene==t.gene&&(r&&!r.has(i.sample)||(o.get(t.gene)[i.sample]=i.value))}});return o}}(t,e),await async function(t,e){const n=t.queries.singleSampleMutation;if(!n)return;if(n.gdcapi)f.validate_query_singleSampleMutation(t,e);else{if(!n.folder)throw"unknown query method for singleSampleMutation";n.get=async e=>{var r,o,i;let s=e;if(null!==(r=t.cohort)&&void 0!==r&&null!==(o=r.termdb)&&void 0!==o&&null!==(i=o.q)&&void 0!==i&&i.sampleName2id&&(s=t.cohort.termdb.q.sampleName2id(e),null==s))return[];const a=await T.read_file(l().join(E().tpmasterdir,n.folder,s.toString()));return JSON.parse(a)}}}(t,e),await async function(t,e){const n=t.queries.singleSampleGenomeQuantification;if(!n)return;for(const r in n){if(!Number.isFinite(n[r].min))throw"min not a number";if(!Number.isFinite(n[r].max))throw"max not a number";if(n[r].min>=n[r].max)throw"min>=max";if(!n[r].folder)throw"unknown query method for singleSampleGenomeQuantification";n[r].get=async(o,i)=>{var s,a,c;let u=o;if(null!==(s=t.cohort)&&void 0!==s&&null!==(a=s.termdb)&&void 0!==a&&null!==(c=a.q)&&void 0!==c&&c.sampleName2id&&(u=t.cohort.termdb.q.sampleName2id(o),null==u))return[];return await ot(l().join(E().tpmasterdir,n[r].folder,u.toString()),e,n[r],i)}}}(t,e),await async function(t,e){const n=t.queries.singleSampleGbtk;if(!n)return;for(const e in n){if(!Number.isFinite(n[e].min))throw"min not a number";if(!Number.isFinite(n[e].max))throw"max not a number";if(n[e].min>=n[e].max)throw"min>=max";if(!n[e].folder)throw"unknown query method for singleSampleGbtk";n[e].get=async r=>{var i,s,a;let c=r;if(null!==(i=t.cohort)&&void 0!==i&&null!==(s=i.termdb)&&void 0!==s&&null!==(a=s.q)&&void 0!==a&&a.sampleName2id&&(c=t.cohort.termdb.q.sampleName2id(r),null==c))return{};const u=l().join(n[e].folder,c+".gz");try{return await o().promises.stat(l().join(E().tpmasterdir,u)),{path:u}}catch(t){return{}}}}}(t),await async function(t,e){const n=t.queries.probe2cnv;if(!n)return;if(n.file)n.file=l().join(E().tpmasterdir,n.file),await T.validate_tabixfile(n.file);else{if(!n.url)throw"file and url both missing on probe2cnv";n.dir=await T.cache_index(n.url,n.indexURL)}n.nochr=await T.tabix_is_nochr(n.file||n.url,null,e);{const e=await T.get_header_tabix(n.file);if(!e[0])throw"header line missing from "+n.file;const r=e[0].split("\t");if(r.length<3)throw"probe2cnv header line less than 3 fields";n.samples=r.slice(2).map((e=>({name:t.cohort.termdb.q.sampleName2id(e)})))}n.get=async e=>{if(!Array.isArray(e.rglst))throw"q.rglst[] is not array";if(0==e.rglst.length)throw"q.rglst[] blank array";if(e.cnvGainCutoff&&!Number.isFinite(e.cnvGainCutoff))throw"cnvGainCutoff is not finite";if(e.cnvLossCutoff&&!Number.isFinite(e.cnvLossCutoff))throw"cnvLossCutoff is not finite";const r=[];{const o=await tt(e,n.samples,t);if(o)for(const[t,e]of n.samples.entries())o.has(e.name)?r.push([]):r.push(null);else for(const t of n.samples)r.push([])}for(const t of e.rglst)await T.get_lines_bigfile({args:[n.file,(n.nochr?t.chr.replace("chr",""):t.chr)+":"+t.start+"-"+t.stop],dir:n.dir,callback:t=>{const e=t.split("\t");for(const[t,n]of r.entries()){if(!n)continue;const r=Number(e[t+2]);Number.isFinite(r)&&n.push(r)}}});const o=[];for(const[t,i]of r.entries()){if(!i)continue;const r=(0,j.Z)(i,50),s={dt:R.dtcnv,value:r,samples:[{sample_id:n.samples[t].name}]};r>0&&r>(e.cnvGainCutoff||.1)?s.class=R.mclasscnvgain:r<0&&r<(e.cnvLossCutoff||-.1)&&(s.class=R.mclasscnvloss),s.class&&o.push(s)}return o}}(t,e),(0,M.validate_variant2samples)(t),function(t){if(!t.ssm2canonicalisoform)return;if(t.ssm2canonicalisoform.gdcapi)return void f.validate_ssm2canonicalisoform(t.ssm2canonicalisoform);throw"ssm2canonicalisoform.gdcapi is false"}(t),function(t,e){if(!e.genedb.hasTable_refseq2ensembl)return;t.refseq2ensembl_query=e.genedb.db.prepare("select ensembl from refseq2ensembl where refseq=?")}(t,e),function(t,e){if(!t.queries.snvindel&&!t.queries.svfusion&&!t.queries.geneCnv)return;t.mayGetGeneVariantData=async(n,r)=>{if("object"!=typeof n.term)throw"tw.term{} is not object";if("geneVariant"!=n.term.type)throw"tw.term.type is not geneVariant";if("string"!=typeof n.term.name)throw"tw.term.name is not string";if(!n.term.name)throw"tw.term.name should be gene symbol but is empty string";const o=[];if(t.queries.snvindel){const i=await async function(t,e,n,r){const o={addFormatValues:!0,filter0:r.filter0,filterObj:r.filter};t.queries.geneCnv&&(o.useCaseid4sample=!0);if(t.queries.snvindel.byisoform)return await async function(t,e){if(t.isoform&&"string"==typeof t.isoform)return;if(!t.name)throw"both term.name and term.isoform";const n=e.genedb.getjsonbyname.all(t.name);if(0==n.length)return;const r=n.find((t=>t.isdefault))||n[0],o=JSON.parse(r.genemodel);if(!o.isoform)throw"isoform missing from returned gm";t.isoform=o.isoform}(e,n),e.isoform?(o.isoform=e.isoform,await t.queries.snvindel.byisoform.get(o)):[];if(t.queries.snvindel.byrange)return await lt(e,n),o.rglst=[e],await t.queries.snvindel.byrange.get(o);throw"unknown queries.snvindel method"}(t,n.term,e,r);o.push(...i)}if(t.queries.svfusion){const i=await async function(t,e,n,r){const o={addFormatValues:!0,filter0:r.filter0,filterObj:r.filter};if(t.queries.svfusion.byrange)return await lt(e,n),o.rglst=[e],await t.queries.svfusion.byrange.get(o);throw"unknown queries.svfusion method"}(t,n.term,e,r);o.push(...i)}if(t.queries.cnv){const i=await async function(t,e,n,r){var o,i,s;const a={addFormatValues:!0,filter0:r.filter0,filterObj:r.filter,cnvMaxLength:null==e||null===(o=e.q)||void 0===o?void 0:o.cnvMaxLength,cnvGainCutoff:null==e||null===(i=e.q)||void 0===i?void 0:i.cnvGainCutoff,cnvLossCutoff:null==e||null===(s=e.q)||void 0===s?void 0:s.cnvLossCutoff};if(t.queries.cnv.byrange)return await lt(e.term,n),a.rglst=[e.term],await t.queries.cnv.byrange.get(a);throw"unknown queries.cnv method"}(t,n,e,r);o.push(...i)}if(t.queries.probe2cnv){const i=await async function(t,e,n,r){var o,i;const s={filter0:r.filter0,filterObj:r.filter,cnvGainCutoff:null==e||null===(o=e.q)||void 0===o?void 0:o.cnvGainCutoff,cnvLossCutoff:null==e||null===(i=e.q)||void 0===i?void 0:i.cnvLossCutoff};return await lt(e.term,n),s.rglst=[e.term],await t.queries.probe2cnv.get(s)}(t,n,e,r);o.push(...i)}if(t.queries.geneCnv){const e=await async function(t,e,n,r){const o={filter0:r.filter0};if(t.queries.geneCnv.bygene)return e.name?(o.gene=e.name,await t.queries.geneCnv.bygene.get(o)):[];throw"unknown queries.geneCnv method"}(t,n.term,0,r);o.push(...e)}const i=new Map;for(const e of o)if(Array.isArray(e.samples))for(const r of e.samples){var s,a;if(i.has(r.sample_id)||i.set(r.sample_id,{sample:r.sample_id}),null!==(s=t.cohort)&&void 0!==s&&null!==(a=s.termdb)&&void 0!==a&&a.additionalSampleAttributes)for(const e of t.cohort.termdb.additionalSampleAttributes)e in r&&(i.get(r.sample_id)[e]=r[e]);i.get(r.sample_id)[n.term.name]||(i.get(r.sample_id)[n.term.name]={key:n.term.name,label:n.term.name,values:[]});const o={gene:n.term.name,isoform:e.isoform,dt:e.dt,chr:n.term.chr,class:e.class,pos:e.pos||(e.start?e.start+"-"+e.stop:""),mname:e.mname,_SAMPLEID_:r.sample_id,_SAMPLENAME_:r.sample_id};if("value"in e&&(o.value=e.value),r.formatK2v)for(const t in r.formatK2v)o[t]=r.formatK2v[t];e.dt==R.dtsnvindel||e.dt==R.dtfusionrna||(e.dt,R.dtsv),t.cohort.termdb.q.id2sampleName&&Number.isInteger(r.sample_id)&&(o._SAMPLENAME_=t.cohort.termdb.q.id2sampleName(r.sample_id)),i.get(r.sample_id)[n.term.name].values.push(o)}return await async function(t,e,n,r){var o;if(null===(o=e.assayAvailability)||void 0===o||!o.byDt)return;const i=t.filter?new Set((await(0,I.get_samples)(t.filter,e)).map((t=>t.id))):null;for(const t in e.assayAvailability.byDt){const o=e.assayAvailability.byDt[t];if(o.byOrigin)for(const e in o.byOrigin){at(t,o.byOrigin[e],n,r,e,i)}else at(t,o,n,r,!1,i)}}(r,t,i,n.term.name),i}}(t,e)),function(t){if(!t.assayAvailability)return;if(t.assayAvailability.byDt)for(const e in t.assayAvailability.byDt){const n=t.assayAvailability.byDt[e];if(n.byOrigin)for(const e in n.byOrigin){const r=n.byOrigin[e];if(!r.yes||!r.no||!r.term_id)throw"ds.assayAvailability.byDt.*.byOrigin properties require .term_id .yes{} .no{}";ct(t,r)}else{if(!n.yes||!n.no||!n.term_id)throw"ds.assayAvailability.byDt properties require .term_id .yes{} .no{}";ct(t,n)}}}(t),null!==(s=t.cohort)&&void 0!==s&&null!==(a=s.db)&&void 0!==a&&a.refresh&&r&&(0,L.setDbRefreshRoute)(t,r,i)}function J(t){var e;const n={isMds3:!0,label:t.label};if(function(t,e){if(!t.queries)return;const n={};t.queries.singleSampleMutation&&(n.singleSampleMutation={sample_id_key:t.queries.singleSampleMutation.sample_id_key,discoSkipChrM:t.queries.singleSampleMutation.discoSkipChrM});if(t.queries.singleSampleGenomeQuantification){n.singleSampleGenomeQuantification={};for(const e in t.queries.singleSampleGenomeQuantification)n.singleSampleGenomeQuantification[e]=JSON.parse(JSON.stringify(t.queries.singleSampleGenomeQuantification[e])),delete n.singleSampleGenomeQuantification[e].folder}if(t.queries.singleSampleGbtk){n.singleSampleGbtk={};for(const e in t.queries.singleSampleGbtk)n.singleSampleGbtk[e]=JSON.parse(JSON.stringify(t.queries.singleSampleGbtk[e])),delete n.singleSampleGbtk[e].folder}const r=t.queries.snvindel;r&&(e.has_skewer=!0,n.snvindel={forTrack:r.forTrack,vcfid4skewerName:r.vcfid4skewerName,variantUrl:r.variantUrl,skewerRim:r.skewerRim},r.m2csq&&(n.snvindel.m2csq={by:r.m2csq.by}),r.info&&(e.bcf={info:r.info}),r.format&&(e.bcf||(e.bcf={}),e.bcf.format=r.format));if(t.queries.ld){n.ld=JSON.parse(JSON.stringify(t.queries.ld));for(const t of n.ld.tracks)delete t.file}e.queries=n}(t,n),null!==(e=t.cohort)&&void 0!==e&&e.termdb&&(n.termdb={},t.cohort.termdb.allowCaseDetails&&(n.termdb.allowCaseDetails={sample_id_key:t.cohort.termdb.allowCaseDetails.sample_id_key})),t.variant2samples){const e=t.variant2samples;n.variant2samples={sunburst_twLst:e.sunburst_twLst,twLst:e.twLst,type_samples:e.type_samples,type_summary:e.type_summary,type_sunburst:e.type_sunburst,url:e.url,variantkey:e.variantkey}}return n}async function W(t){var e,r,o,i;if(t.cohort){if(!t.cohort.termdb)throw"ds.cohort is set but cohort.termdb{} missing";if(!t.cohort.db)throw"ds.cohort is set but cohort.db{} missing";if(!t.cohort.db.file&&!t.cohort.db.file_fullpath)throw"ds.cohort.db.file missing"}else{if(!t.termdb)return;t.cohort={},t.cohort.termdb=t.termdb,delete t.termdb}const s=t.cohort.termdb;if(null!=s&&null!==(e=s.dictionary)&&void 0!==e&&e.gdcapi)await x(t);else if(null!=s&&null!==(r=s.dictionary)&&void 0!==r&&r.dbFile)t.cohort.db={file:s.dictionary.dbFile},delete s.dictionary.dbFile,(0,P.server_init_db_queries)(t);else{if(!t.cohort.db)throw"unknown method to initiate dictionary";(0,P.server_init_db_queries)(t)}if(s.termid2totalsize2&&(s.termid2totalsize2.gdcapi,s.termid2totalsize2.get=async(e,n={},r=null)=>s.termid2totalsize2.gdcapi?await f.get_termlst2size(e,n,r,t):await async function(t,e,n,r){const o=new Map;for(const n of t)if(n.term&&"categorical"==n.term.type){var i,s;const t={term1_id:n.id,term1_q:{type:"values"}};e.tid2value&&(t.filter=et(e.tid2value,r));const a=await(0,F.barchart_data)(t,r,r.cohort.termdb);if(null==a||null===(i=a.data)||void 0===i||null===(s=i.charts)||void 0===s||!s[0])continue;const l=[];for(const t of a.data.charts[0].serieses)l.push([t.seriesId,t.total]);o.set(n.id,l)}return n?[o,n]:o}(e,n,r,t)),function(t){const e=t.selectCohort;if(!e)return;if("object"!=typeof e)throw"selectCohort{} not object";if(!e.term)throw"term{} missing from termdb.selectCohort";if(!e.term.id)throw"id missing from termdb.selectCohort.term";if("string"!=typeof e.term.id)throw"termdb.selectCohort.term.id is not string";if("categorical"!=e.term.type)throw'type is not hardcoded "categorical" from termdb.selectCohort.term';{const n=t.q.termjsonByOneid(e.term.id);if(!n)throw"termdb.selectCohort.term.id is invalid";if("categorical"!=n.type)throw"termdb.selectCohort.term type is not categorical"}if(!e.values)throw"values[] missing from termdb.selectCohort";if(!Array.isArray(e.values))throw"termdb.selectCohort.values is not array";if(0==e.values.length)throw"termdb.selectCohort.values[] cannot be empty";for(const t of e.values){if(!t.keys)throw"keys[] missing from one of selectCohort.values[]";if(!Array.isArray(t.keys))throw"keys[] is not array from one of selectCohort.values[]";if(0==t.keys.length)throw"keys[] is empty from one of selectCohort.values[]"}}(s),await async function(t){if(!t.restrictAncestries)return;if(!Array.isArray(t.restrictAncestries)||0==t.restrictAncestries.length)throw"termdb.restrictAncestries[] is not non-empty array";for(const e of t.restrictAncestries){if(!e.name)throw"name missing from one of restrictAncestries";if("object"!=typeof e.tvs)throw".tvs{} missing from one of restrictAncestries";if(!e.tvs.term)throw"tvs.term{} missing from an ancestry";if(!e.tvs.term.id)throw"tvs.term.id missing from an ancestry";{const n=t.q.termjsonByOneid(e.tvs.term.id);if(!n)throw"tvs.term.id is invalid from an ancestry";if("categorical"!=n.type)throw"tvs.term.type is not categorical from an ancestry"}if(!Number.isInteger(e.PCcount))throw"PCcount is not integer";if(e.PCfile)e.pcs=await H(e.PCfile,e.PCcount);else if(e.PCfileBySubcohort){if(!t.selectCohort)throw"PCfileBySubcohort is in use but selectCohort is not enabled";for(const n in e.PCfileBySubcohort){let r=!0;for(const e of t.selectCohort.values)if(n==e.keys.sort().join(",")){r=!1;break}if(r)throw"unknown subcohort from PCfileBySubcohort";const o=e.PCfileBySubcohort[n];if(!o.file)throw".file missing for a subcohort in PCfileBySubcohort";o.pcs=await H(o.file,e.PCcount)}}}}(s),await(0,D.wz)(t),await(0,B.mayInitiateMatrixplots)(t),"minTimeSinceDx"in s){if(!Number.isFinite(s.minTimeSinceDx))throw"termdb.minTimeSinceDx not number";if(s.minTimeSinceDx<=0)throw"termdb.minTimeSinceDx<=0"}if("ageEndOffset"in s){if(!Number.isFinite(s.ageEndOffset))throw"termdb.ageEndOffset not number";if(s.ageEndOffset<=0)throw"termdb.ageEndOffset<=0"}if(t.cohort.termdb.additionalSampleAttributes){if(!Array.isArray(t.cohort.termdb.additionalSampleAttributes))throw"termdb.additionalSampleAttributes not array";for(const e of t.cohort.termdb.additionalSampleAttributes)if("string"!=typeof e)throw"non-str key in termdb.additionalSampleAttributes[]"}if(null!==(o=t.cohort)&&void 0!==o&&null!==(i=o.db)&&void 0!==i&&i.connection){t.sampleName2Id=new Map,t.sampleId2Name=new Map;const e="SELECT * FROM sampleidmap",n=t.cohort.db.connection.prepare(e).all();for(const e of n)t.sampleId2Name.set(e.id,e.name),t.sampleName2Id.set(e.name,e.id);t.getSampleIdMap=e=>{const n={};for(const r in e)n[r]=t.sampleId2Name.get(+r);return n}}if(t.cohort.mutationset){const{mayGetGeneVariantData:e,getTermTypes:r,mayGetMatchingGeneNames:o}=n(7833);t.mayGetGeneVariantData=e,t.getTermTypes=r,t.mayGetMatchingGeneNames=o}}async function H(t,e){const n=new Map;for(let t=1;t<=e;t++)n.set($+t,new Map);let r=0;for(const o of(await T.read_file(l().join(E().tpmasterdir,t))).trim().split("\n")){r++;const t=o.split("\t"),i=Number(t[0]);if(!Number.isInteger(i))throw"non-integer sample id from a line of restrictAncestries pc file";for(let r=1;r<=e;r++){const e=$+r,o=Number(t[r]);if(Number.isNaN(o))throw"non-numeric PC value from restrictAncestries file";n.get(e).set(i,o)}}return console.log(r,"samples loaded from "+t),Object.freeze(n)}function V(t,e,n){var r;if(!e)return;let o;if(null!=t&&null!==(r=t.cohort)&&void 0!==r&&r.termdb){for(const t of e){const e=Number(t.name);if(!Number.isInteger(e))throw"non-integer sample id from "+n;t.name=e}o=", all integer IDs"}console.log(e.length,"samples from "+n+" of "+t.label+o)}async function Y(t,e){var n;const r=t.queries.snvindel.byrange;if(r._tk.file)await T.init_one_vcf(r._tk,e,!0);else if(r._tk.chr2files){let t;for(const n in r._tk.chr2files){if("chr17"!=n)continue;const o=r._tk.chr2files[n];try{await T.init_one_vcf(o,e,!0);const i=JSON.stringify(o.samples);if(t){if(i!=t)throw"Different samples found in bcf file of "+n}else t=i,r._tk.samples=o.samples,r._tk.format=o.format,r._tk.info=o.info,r._tk.nochr=o.nochr}catch(t){console.log("missing file ignored:",o.file)}}}if(null!==(n=r._tk)&&void 0!==n&&n.samples.length){if(!r._tk.format)throw"bcf file has samples but no FORMAT"}else if(r._tk.format)throw"bcf file has FORMAT but no samples";if(r._tk.format){for(const t in r._tk.format)"GT"==t&&(r._tk.format[t].isGT=!0);if(t.queries.snvindel.format4filters){if(!Array.isArray(t.queries.snvindel.format4filters))throw"snvindel.format4filters[] is not array";for(const e of t.queries.snvindel.format4filters)r._tk.format[e]&&(r._tk.format[e].isFilter=!0);delete t.queries.snvindel.format4filters}}if(r._tk.info){if(r.infoFields){for(const t of r.infoFields){if(!t.key)throw".key missing from one of snvindel.byrange.infoFields[]";t.name||(t.name=t.key);const e=r._tk.info[t.key];if(!e)throw"invalid key from one of snvindel.byrange.infoFields[]";e.categories=t.categories,e.name=t.name,e.separator=t.separator}delete r.infoFields}if(t.queries.snvindel.infoUrl){for(const e of t.queries.snvindel.infoUrl){const t=r._tk.info[e.key];if(!t)throw"invalid key from one of snvindel.infoUrl[]";t.urlBase=e.base}delete t.queries.snvindel.infoUrl}}return t.queries.snvindel.info=r._tk.info,t.queries.snvindel.format=r._tk.format,async e=>{if(!Array.isArray(e.rglst))throw"q.rglst[] is not array";if(0==e.rglst.length)throw"q.rglst[] blank array";const n=Q(e);let o;if(r._tk.chr2files){const t=r._tk.chr2files[e.rglst[0].chr];if(!t)throw"unknown chr for chr2files";o=t.file}else o=r._tk.file||r._tk.url;const i=["query",o,"-r",e.rglst.map((t=>(r._tk.nochr?t.chr.replace("chr",""):t.chr)+":"+t.start+"-"+(t.stop+1))).join(","),"-f","%ID\t%CHROM\t%POS\t%REF\t%ALT\t%INFO\t%FORMAT\n"],s=await tt(e,r._tk.samples,t);s&&i.push("-s",[...s].join(",")),e.variantFilter&&(0,z.add_bcf_variant_filter)(e.variantFilter,i);const a=[];return await T.get_lines_bigfile({isbcf:!0,args:i,dir:r._tk.dir,callback:o=>{const i=o.split("\t"),l=i[0],c=i[1],u=Number(i[2]),f=i[3],d=i[4].split(","),h=i[5],p={pos:u-1};(0,C.compute_mclass)(r._tk,f,d,p,h,l,e.isoform);for(const o of p.mlst){var m,g,y;e.hiddenmclass&&e.hiddenmclass.has(o.class)||(K(o,e)||p.mlst.length>1&&null!==(m=e.variantFilter)&&void 0!==m&&m.lst&&X(o,e)||(o.chr=(r._tk.nochr?"chr":"")+c,o.ssm_id=[o.chr,o.pos,o.ref,o.alt].join(Z),null!==(g=r._tk)&&void 0!==g&&null!==(y=g.samples)&&void 0!==y&&y.length&&(nt(r,o,i,e.addFormatValues,t,s,n),!o.samples)||a.push(o)))}}}),a}}function Q(t){var e,n;const r=t.formatFilter||{};return"format"==(null===(e=t.skewerRim)||void 0===e?void 0:e.type)&&null!==(n=t.skewerRim.hiddenvalues)&&void 0!==n&&n.size&&(r[t.skewerRim.formatKey]=t.skewerRim.hiddenvalues),Object.keys(r).length?r:void 0}function K(t,e){if(!e.infoFilter)return!1;for(const n in e.infoFilter){const r=t.info[n];if(r)if(Array.isArray(r)){for(const t of e.infoFilter[n])if(r.includes(t))return!0}else if(e.infoFilter[n].includes(r))return!0}return!1}function X(t,e){for(const r of e.variantFilter.lst){const e=t.info[r.tvs.term.id];if(null==e)return!0;if("integer"==r.tvs.term.type||"float"==r.tvs.term.type){var n;const t=Number(e);if(Number.isNaN(t))return!0;const o=null===(n=r.tvs.ranges)||void 0===n?void 0:n[0];if(o){if("start"in o)if(o.startinclusive){if(t<o.start)return!0}else if(t<=o.start)return!0;if("stop"in o)if(o.stopinclusive){if(t>o.stop)return!0}else if(t>=o.stop)return!0}}}return!1}async function tt(t,e,n){if(!e)return;const r=function(t,e){if(t.filterObj){if(!Array.isArray(t.filterObj.lst))throw"filterObj.lst is not array";return 0==t.filterObj.lst.length?null:t.filterObj}if(t.tid2value){if("object"!=typeof t.tid2value)throw"q.tid2value{} not object";return et(t.tid2value,e)}}(t,n);if(!r)return;const o=[...new Set((await(0,I.get_samples)(r,n)).map((t=>t.id)))],i=new Set(e.map((t=>t.name))),s=new Set;for(const t of 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0!==b&&null!==(_=b.svfusion)&&void 0!==_&&null!==(w=_.byrange)&&void 0!==w&&w.samples&&(e=!0),!e)throw"cannot find a sample source from ds.queries{}"}if(e.get=async e=>await async function(t,e){!function(t,e){if("samples"==t.get){var n,r;const o=null===(n=e.queries)||void 0===n||null===(r=n.snvindel)||void 0===r?void 0:r.byrange;o&&(o.bcffile||o.chr2bcffile)&&o._tk.format&&(t.addFormatValues=!0)}}(t,e);const n=await async function(t,e){var n;const r=t.twLst?t.twLst.slice():[];if(e.variant2samples.gdcapi)return await o(t,r,e,t.geneTwLst);if(t.ssm_id_lst)return await async function(t,e,n){const r=new Map;for(const e of t.ssm_id_lst.split(",")){const o=e.split(s);if(4!=o.length){if(6!=o.length)throw"unknown format of ssm id";{if(!n.queries.svfusion||!n.queries.svfusion.byrange)throw"queries.svfusion.byrange missing when id has 6 fields";const[e,i,s,c,u,f]=o,h=decodeURIComponent(f),p=Number(e);if(p!=l&&p!=a)throw"dt not sv/fusion";const m=Number(s);if(Number.isNaN(m))throw"position not 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n=c.getResult(t.genome,{deep:1,input:e.term.name});if(n.gmlst){const e=n.gmlst[0];t.rglst.push({chr:e.chr,start:e.start,stop:e.stop})}}const n=await p(t,r,e);return delete t.rglst,n}if(null==e||null===(n=e.cohort)||void 0===n||!n.termdb)throw"unable to do sql query: .cohort.termdb missing for ds";const i={ds:e,filter:t.filter||t.filterObj},f=await u(i,t.twLst),m=[];for(const e in f.samples){const n=f.samples[e];n.sample_id=n.sample,delete n.sample;for(const e of t.twLst)n[e.term.id]&&(n[e.term.id]=n[e.term.id].key);m.push(n)}return m}(t,e);if(t.get==e.variant2samples.type_samples){var f,y,v;return!t.useIntegerSampleId&&null!=e&&null!==(f=e.cohort)&&void 0!==f&&null!==(y=f.termdb)&&void 0!==y&&null!==(v=y.q)&&void 0!==v&&v.id2sampleName&&n.forEach((t=>t.sample_id=e.cohort.termdb.q.id2sampleName(t.sample_id))),n}if(t.get==e.variant2samples.type_sunburst)return await async function(t,e,n){var o,i;const s=r(t,n.twLst.map((t=>({k:t.id}))));for(const t of s)delete t.lst;if(null!=e&&null!==(o=e.cohort)&&void 0!==o&&null!==(i=o.termdb)&&void 0!==i&&i.termid2totalsize2){const t=await g(n.twLst,e,n,s);await async function(t,e,n){for(const r of t){if(!r.id0)continue;if(!r.v0)continue;const t=n.cohort.termdb.useLower?r.v0.toLowerCase():r.v0;if(!r.id1){const n=e.find((e=>null==e.id1&&e.v0==t));n&&(r.cohortsize=n.count);continue}if(!r.v1)continue;const o=n.cohort.termdb.useLower?r.v1.toLowerCase():r.v1;if(!r.id2){const n=e.find((e=>null==e.id2&&e.v0==t&&e.v1==o));n&&(r.cohortsize=n.count);continue}if(!r.v2)continue;const i=n.cohort.termdb.useLower?r.v2.toLowerCase():r.v2;if(!r.id3){const e=crosstabL2.find((e=>e.v0==t&&e.v1==o&&e.v2==i));e&&(r.cohortsize=e.count)}}}(s,t,e)}return s}(n,e,t);if(t.get==e.variant2samples.type_summary){const r=await async function(t,e,n){if(!n.twLst)throw"q.twLst[] missing for make_summary()";const r=[];for(const e of n.twLst)if(e.term)if("categorical"==e.term.type){const 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c)"*"===t&&(c[""]=c[t],delete c[t]);for(const t in c)for(const e in c[t].estimates)"*"===e&&(c[t].estimates[""]=c[t].estimates[e],delete c[t].estimates[e]);for(const t in c){for(const n in c[t].estimates){const r=c[t].estimates[n];for(let o=0;o<r.length;o++)e.case.push([t,n,r[o].time,r[o].est,r[o].low,r[o].up,r[o].nrisk,r[o].nevent,r[o].ncensor])}c[t].tests&&(e.tests||(e.tests={}),e.tests[t]=c[t].tests)}s.unlink(n,(()=>{}))}},5257:(t,e)=>{function n(t,e){return{CTEs:[`\n\t\t ${e} AS (\n\t\t\t\tSELECT sample\n\t\t\t\tFROM anno_categorical\n\t\t\t\tWHERE term_id = ?\n\t\t\t\tAND value ${t.isnot?"NOT":""} IN (${t.values.map((t=>"?")).join(", ")})\n\t\t\t)`],values:[t.term.id,...t.values.map((t=>t.key))],CTEname:e}}function r(t,e){var n,r;return{CTEs:[`\n\t\t ${e} AS (\n\t\t\t\tSELECT sample\n\t\t\t\tFROM survival\n\t\t\t\tWHERE term_id = ?\n\t\t\t\t${null!==(n=t.q)&&void 0!==n&&n.cutoff?"AND tte >= "+(null===(r=t.q)||void 0===r?void 0:r.cutoff):""}\n\t\t\t\tAND exit_code ${t.isnot?"NOT":""} IN (${t.values.map((t=>"?")).join(", ")})\n\t\t\t)`],values:[t.term.id,...t.values.map((t=>t.key))],CTEname:e}}function o(t,e){const n=[];for(const e in t.term.values)n.push(...t.term.values[e].list);return{CTEs:[`\n\t\t ${e} AS (\n\t\t\t\tSELECT id as sample\n\t\t\t\tFROM sampleidmap\n\t\t\t\tWHERE id IN (${Array(n.length).fill("?").join(", ")})\n\t\t\t)`],values:[...n.map((t=>t.sampleId))],CTEname:e}}async function i(t,e,n){const r={term:t.term,q:{}},o=await n.mayGetGeneVariantData(r,{genome:n.genomename}),i=[];for(const[e,n]of o){const r=n[t.term.name].values;let o=!0;for(const e of t.values){const t=r.filter((t=>t.dt==e.dt&&(!e.origin||e.origin==t.origin)));for(const n of t)if(e.mclassExcludeLst.includes(null==n?void 0:n.class)){o=!1;break}}o&&i.push(e)}return{CTEs:[`\n\t\t ${e} AS (\n\t\t\t\tSELECT id as sample\n\t\t\t\tFROM sampleidmap\n\t\t\t\tWHERE id IN (${i.map((t=>"?")).join(", ")})\n\t\t\t)`],values:[...i],CTEname:e}}function s(t,e,n){if(!t.ranges)throw".ranges{} missing";const r=[t.term.id],o=n.cohort.termdb.q.termjsonByOneid(t.term.id),i=[];let s,a=!1;for(const e of t.ranges)if("value"in e){const n=t.isnot?"!":"";i.push(`value ${n}= ?`),r.push(""+e.value)}else{a=!0;const n=[];e.startunbounded||(e.startinclusive?n.push("value >= ?"):n.push("value > ? 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"),r.push(e.stop));const o=t.isnot?"NOT ":"";n.length&&i.push(o+"("+n.join(" AND ")+")")}a&&o.values&&(s=Object.keys(o.values).filter((t=>o.values[t].uncomputable)).map(Number).filter((e=>t.isnot||!t.ranges.find((t=>"value"in t&&Number(t.value)==e)))),s.length&&r.push(...s));const l=i.join(" OR ");return{CTEs:[`\n\t\t ${e} AS (\n\t\t\t\tSELECT sample\n\t\t\t\tFROM anno_${o.type}\n\t\t\t\tWHERE term_id = ?\n\t\t\t\t${l?"AND ("+l+")":""}\n\t\t\t\t${s&&s.length?`AND value NOT IN (${s.map((t=>"?")).join(",")})`:""}\n\t\t\t)`],values:r,CTEname:e}}function a(t,e){let n,r;if(t.bar_by_children)n="child";else{if(!t.bar_by_grade)throw"must set the bar_by_grade or bar_by_children query parameter";n="grade"}if(t.value_by_max_grade)r="max_grade";else if(t.value_by_most_recent)r="most_recent";else{if(!t.value_by_computable_grade)throw"unknown setting of value_by_?";r="computable_grade"}const o=[],i=[];if(!t.values)throw t.grade_and_child?"-- Todo: tvs.grade_and_child":'unknown condition term filter 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e=c+"_"+h;let m;if("tvslst"==p.type)m=await t(p,l,e);else if("categorical"==p.tvs.term.type)m=n(p.tvs,e);else if("survival"==p.tvs.term.type)m=r(p.tvs,e);else if("samplelst"==p.tvs.term.type)m=o(p.tvs,e);else if("integer"==p.tvs.term.type||"float"==p.tvs.term.type)m=s(p.tvs,e,l);else if("condition"==p.tvs.term.type)m=a(p.tvs,e);else{if("geneVariant"!=p.tvs.term.type)throw"unknown term type";m=await i(p.tvs,e,l)}u.push(m.CTEname),f.push(...m.CTEs),d.push(...m.values)}const h="and"==e.join?"INTERSECT":"UNION",p=u.map((t=>"SELECT * FROM "+t)).join("\n"+h+"\n");return e.in?f.push(`\n\t\t\t\t${c} AS (\n\t\t\t\t\t${p}\n\t\t\t\t)\n\t\t\t`):f.push(`\n\t\t\t\t${c} AS (\n\t\t\t\t\tSELECT id as sample\n\t\t\t\t\tFROM sampleidmap\n\t\t\t\t\tWHERE sample NOT IN (\n\t\t\t\t\t\t${p}\n\t\t\t\t\t)\n\t\t\t\t)\n\t\t\t`),{filters:f.join(",\n"),CTEs:f,values:d,CTEname:c}}},7860:(t,e,n)=>{"use strict";n.r(e),n.d(e,{copy_term:()=>S,handle_request_closure:()=>N});var r=n(5684),o=n(7027),i=n(3856),s=n(6191),a=n.n(s),l=n(4065);const c=n(5174),u=n(2852),f=n(5708),d=n(4453),h=n(1468),p=n(8599),m=n(3795),g=n(1711).getOrderedLabels,y=n(1575).CG,v=n(2188).uR,b=n(2188).v8,_=n(4603).g,w=n(2974).getData,x=n(601).v,k=n(4143).R,q=10;function N(t){return async(e,n)=>{const s=e.query;try{const N=t[s.genome];if(!N)throw"invalid genome";const[M,T]=function(t,e){{const r=t.datasets[e.dslabel];if(r){var n;if(null!=r&&null!==(n=r.cohort)&&void 0!==n&&n.termdb)return[r,r.cohort.termdb];throw".cohort.termdb not found on this dataset"}}if(!t.termdbs)throw"genome-level termdb not available";const r=t.termdbs[e.dslabel];if(!r)throw"invalid dslabel";if(!r.cohort)throw"ds.cohort missing for genome-level termdb";if(!r.cohort.termdb)throw"ds.cohort.termdb{} missing for a genome-level termdb";return[r,r.cohort.termdb]}(N,s);if(s.gettermbyid)return function(t,e,n){const r=n.q.termjsonByOneid(t.gettermbyid);e.send({term:r?S(r):void 0})}(s,n,T);if(s.getcategories)return await async function(t,e,n,r,o){var i,s,a;if(!t.tid)throw".tid missing";const l="geneVariant"==t.type?{name:t.tid,type:"geneVariant",isleaf:!0}:n.q.termjsonByOneid(t.tid),c={filter:t.filter,terms:"geneVariant"==t.type?[{term:l,q:{isAtomic:!0}}]:[{id:t.tid,term:l,q:t.term1_q||A(l,t)}],currentGeneNames:t.currentGeneNames},u=await w(c,r,o);if(u.error)throw u.error;const f=[];if("geneVariant"==t.type){var d;const e=u.samples,n=new Map;if(null!==(d=r.assayAvailability)&&void 0!==d&&d.byDt)for(const[t,e]of Object.entries(r.assayAvailability.byDt))e.byOrigin&&n.set(parseInt(t),{byOrigin:{germline:{},somatic:{}}});for(const[r,o]of Object.entries(e)){const e=o[t.tid].values;for(const t of e){n.has(t.dt)||n.set(t.dt,{});const e=n.get(t.dt);e.byOrigin?e.byOrigin[t.origin][t.class]=e.byOrigin[t.origin][t.class]?e.byOrigin[t.origin][t.class]+1:1:e[t.class]=e[t.class]?e[t.class]+1:1}}for(const[t,e]of n)f.push({dt:t,classes:e})}else{const e=new Map;for(const n in u.samples){const r=u.samples[n][t.tid];r&&("key"in r&&e.set(r.key,1+(e.get(r.key)||0)))}for(const[n,r]of e){var h,p,m,y;f.push({samplecount:r,key:"cox"==(null===(h=t.term1_q)||void 0===h?void 0:h.mode)?JSON.parse(n).event:n,label:"cox"==(null===(p=t.term1_q)||void 0===p?void 0:p.mode)?JSON.parse(n).label:(null==l||null===(m=l.values)||void 0===m||null===(y=m[n])||void 0===y?void 0:y.label)||n})}}const v=g(l,(null===(i=u.refs)||void 0===i||null===(s=i.byTermId)||void 0===s||null===(a=s[t.tid])||void 0===a?void 0:a.bins)||[],t.term1_q);v.length&&f.sort(((t,e)=>v.indexOf(t.label)-v.indexOf(e.label)));e.send({lst:f,orderedLabels:v})}(s,n,T,M,N);if(s.getpercentile)return async function(t,e,n){const r=n.cohort.termdb.q.termjsonByOneid(t.tid);if(!r)throw"invalid termid";if("float"!=r.type&&"integer"!=r.type)throw"not numerical term";const i=t.getpercentile,s=[],a=[],l=await u.get_rows_by_one_key({ds:n,key:t.tid,filter:t.filter?"string"==typeof t.filter?JSON.parse(t.filter):t.filter:null});for(const{value:t}of l)r.values&&r.values[t]&&r.values[t].uncomputable||r.skip0forPercentile&&0==t||a.push(Number(t));for(const t of i){const e=(0,o.Z)(a,t);s.push(e)}e.send({values:s})}(s,n,M);if(s.getdescrstats)return async function(t,e,n){const i=n.cohort.termdb.q.termjsonByOneid(t.tid);if(!i)throw"invalid termid";if("float"!=i.type&&"integer"!=i.type)throw"not numerical term";const s=await u.get_rows_by_one_key({ds:n,key:t.tid,filter:t.filter?"string"==typeof t.filter?JSON.parse(t.filter):t.filter:null}),a=[];for(const{value:e}of s){var l,c;i.values&&i.values[e]&&i.values[e].uncomputable||("log"===(null===(l=t.settings)||void 0===l||null===(c=l.violin)||void 0===c?void 0:c.unit)&&0===e||a.push(Number(e)))}const f=a.length,d=a.reduce(((t,e)=>t+e),0)/f,h=(0,o.Z)(a,25),p=(0,o.Z)(a,50),m=(0,o.Z)(a,75),g=a.map((t=>(t-d)**2)).reduce(((t,e)=>t+e),0)/(a.length-1),y=Math.sqrt(g),v=Math.min(...a),b=Math.max(...a);e.send({values:[{id:"total",label:"n",value:f},{id:"min",label:"Minimum",value:(0,r.Z)(v,2)},{id:"p25",label:"1st quartile",value:(0,r.Z)(h,2)},{id:"median",label:"Median",value:(0,r.Z)(p,2)},{id:"mean",label:"Mean",value:(0,r.Z)(d,2)},{id:"p75",label:"3rd quartile",value:(0,r.Z)(m,2)},{id:"max",label:"Maximum",value:(0,r.Z)(b,2)},{id:"sd",label:"Standard deviation",value:(0,r.Z)(y,2)}]})}(s,n,M);if(s.getnumericcategories)return await async function(t,e,n,r){if(!t.tid)throw".tid missing";n.q.termjsonByOneid(t.tid);const o={ds:r,term_id:t.tid};t.filter&&(o.filter=t.filter);const i=await u.get_summary_numericcategories(o);e.send({lst:i})}(s,n,T,M);if(s.default_rootterm)return await async function(t,e,n){const r=t.cohortValues?t.cohortValues:"",o=t.treeFilter?t.treeFilter:"";e.send({lst:await n.q.getRootTerms(r,o)})}(s,n,T);if(s.get_children)return await async function(t,e,n){if(!t.tid)throw"no parent term id";const r=t.cohortValues?t.cohortValues:"",o=t.treeFilter?t.treeFilter:"",i=await n.q.getTermChildren(t.tid,r,o);e.send({lst:i.map(S)})}(s,n,T);if(s.findterm)return await async function(t,e,n,r,o){var i;const s={equals:[],startsWith:[],startsWord:[],includes:[]},a=decodeURIComponent(t.findterm).toUpperCase(),c=y({type:"geneVariant"},t.usecase).has("plot");r.mayGetMatchingGeneNames&&c&&await r.mayGetMatchingGeneNames(s,a,t);const u=[];if(null!==(i=r.queries)&&void 0!==i&&i.defaultBlock2GeneMode&&c){const t=(0,l.getResult)(o,{input:a});if(Array.isArray(t.hits))for(let e=0;e<7&&t.hits[e];e++)u.push({name:t.hits[e],type:"geneVariant"})}"string"!=typeof t.cohortStr&&(t.cohortStr="");const f=await n.q.findTermByName(a,q,t.cohortStr,t.treeFilter,t.usecase,s);u.push(...f.map(S));u.forEach((t=>{"geneVariant"!=t.type&&(t.__ancestors=n.q.getAncestorIDs(t.id),t.__ancestorNames=n.q.getAncestorNames(t.id))})),e.send({lst:u})}(s,n,T,M,N);if(s.getterminfo)return function(t,e,n){if(!t.tid)throw"no term id";e.send({terminfo:n.q.getTermInfo(t.tid)})}(s,n,T);if(s.phewas)return s.update?await f.update_image(s,n):s.getgroup?await f.getgroup(s,n):await f.trigger(s,n,M);if(s.gettermdbconfig)return c.make(s,n,M,N);if(s.getcohortsamplecount)return n.send({count:M.cohort.termdb.q.getcohortsamplecount(s.cohort)});if(s.getsamplecount)return n.send(await async function(t,e,n){const r=a().canDisplaySampleIds(t,n);if("list"==e.getsamplecount){return await u.get_samples(e.filter,n,r)}return await u.get_samplecount(e,n)}(e,s,M));if(s.getsamples)return await async function(t,e,n){const r=await u.get_samples(t.filter,n),o=r.map((t=>n.cohort.termdb.q.id2sampleName(t)));e.send({samples:o})}(s,n,M);if(s.getcuminc)return await async function(t,e,n){if(!t.minSampleSize)throw"missing minSampleSize";t.minSampleSize=Number(t.minSampleSize);const r=await d.get_incidence(t,n);e.send(r)}(s,n,M);if(s.getsurvival)return await async function(t,e,n){const r=await h.get_survival(t,n);e.send(r)}(s,n,M);if(s.getregression)return await async function(t,e,n){const r=await p.get_regression(t,n);e.send(r)}(s,n,M);if(s.validateSnps)return n.send(await m.validate(s,T,M,N));if(s.getvariantfilter)return function(t,e){var n,r;if(e.track)return void t.send(e.track.variant_filter);t.send((null==e||null===(n=e.queries)||void 0===n||null===(r=n.snvindel)||void 0===r?void 0:r.variant_filter)||{})}(n,M);if(s.getLDdata)return await async function(t,e,n){var r,o;if(!t.ldtkname)throw".ldtkname missing";if(null===(r=e.queries)||void 0===r||null===(o=r.ld)||void 0===o||!o.tracks)throw"no ld tk";const s=e.queries.ld.tracks.find((e=>e.name==t.ldtkname));if(!s)throw"unknown ld tk";if("object"!=typeof t.m)throw"q.m{} not object";if(!t.m.chr)throw"q.m.chr missing";if(!Number.isInteger(t.m.pos))throw"q.m.pos not integer";if(!t.m.ref||!t.m.alt)throw"q.m{} invalid alleles";const a=t.m.ref+"."+t.m.alt,l=(s.nochr?t.m.chr.replace("chr",""):t.m.chr)+":"+t.m.pos+"-"+(t.m.pos+1),c=[];await(0,i.get_lines_bigfile)({args:[s.file,l],dir:s.dir,callback:e=>{const n=e.split("\t"),r=Number.parseInt(n[1]),o=Number.parseInt(n[2]),i=n[3],s=n[4],l=Number.parseFloat(n[5]);r==t.m.pos&&i==a?c.push({pos:o,alleles:s,r2:l}):o==t.m.pos&&s==a&&c.push({pos:r,alleles:i,r2:l})}}),n.send({lst:c})}(s,M,n);if(s.genesetByTermId)return function(t,e,n){if(!n.termMatch2geneSet)throw"this feature is not enabled";if("string"!=typeof t.genesetByTermId||0==t.genesetByTermId.length)throw"invalid query term id";const r=n.q.getGenesetByTermId(t.genesetByTermId);e.send(r)}(s,n,T);if(s.getSampleScatter)return await v(e,s,n,M,N);if(s.getLowessCurve)return await b(e,s,n);if(s.getCohortsData)return await x(s,n,M);if(s.getViolinPlotData)return await _(s,n,M,N);if("mds3queryDetails"==s.for)return function(t,e){const n={},r=e.queries||{};r.snvindel&&(n.snvindel={},r.snvindel.details&&(n.snvindel.details=r.snvindel.details),r.snvindel.populations&&(n.snvindel.populations=r.snvindel.populations));r.trackLst&&(n.trackLst=r.trackLst);if(r.ld){n.ld=JSON.parse(JSON.stringify(r.ld));for(const t of n.ld.tracks)delete t.file}t.send(n)}(n,M);if("termTypes"==s.for)return n.send(await M.getTermTypes(s));if("matrix"==s.for)return await async function(t,e,n,r,o){if(t.getPlotDataByName){if(!r.cohort.matrixplots)throw"ds.cohort.matrixplots missing for the dataset";if(!r.cohort.matrixplots.plots)throw"ds.cohort.matrixplots.plots missing for the dataset";const e=r.cohort.matrixplots.plots.find((e=>e.name===t.getPlotDataByName));if(!e)throw`plot name: q.getPlotDataByName=${getPlotDataByName} missing in ds.cohort.matrixplots.plots`;return void n.send(e.matrixConfig)}const i=await w(t,r,o);if(a().canDisplaySampleIds(e,r))for(const t of Object.values(i.samples))t.sampleName=r.sampleId2Name.get(t.sample);n.send(i)}(s,e,n,M,N);if("mds3variantData"==s.for)return await k(s,n,M,N);throw s.for,"termdb: doesn't know what to do"}catch(t){n.send({error:t.message||t}),t.stack?console.log(t.stack):console.log(t)}}}function S(t){return JSON.parse(JSON.stringify(t))}function A(t,e){if("categorical"==t.type)return{};if("survival"==t.type)return{};if("integer"==t.type||"float"==t.type)return t.bins.default;if("condition"==t.type)return{mode:e.mode,breaks:e.breaks,bar_by_grade:e.bar_by_grade,bar_by_children:e.bar_by_children,value_by_max_grade:e.value_by_max_grade,value_by_most_recent:e.value_by_most_recent,value_by_computable_grade:e.value_by_computable_grade};if("geneVariant"==t.type)return{};throw"unknown term type"}},2974:(t,e,n)=>{"use 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i={age_start:r,age_end:"age"==t.outcome.q.timeScale?o+f:o};u.push({sample:e.sample,key:n,value:i,term_id:e.term_id})}else u.push(e);for(const{sample:t,term_id:r,key:o,value:i}of u){const s=e.find((t=>t.id==r));if(n.has(t)||n.set(t,{sample:t,id2value:new Map}),n.get(t).id2value.has(r))throw`duplicate '${r}' entry for sample='${t}'`;n.get(t).id2value.set(r,{key:s.q.scale?o/s.q.scale:o,value:s.q.scale?i/s.q.scale:i})}const d=new Set;for(const t of n.values())for(const n of e)if(!t.id2value.has(n.id)){d.add(t.sample);break}for(const t of d)n.delete(t);return n}(t,r);for(const t of s){if(A(t,a,n),"snplst"!=t.type&&"snplocus"!=t.type)throw"unknown type of independent non-dictionary term";await M(t,a)}return[...a.values()]}(t,[t.outcome,...t.independent],e);y=(new Date).getTime(),v.NodeJS.getSampleData=(y-g)/1e3+" sec",g=(new Date).getTime();const r=function(t,e){const n={id:t.outcome.id,name:t.outcome.term.name,rtype:"numeric"};"logistic"==t.regressionType&&(n.categories={ref:t.outcome.refGrp,nonref:k(t.outcome)});"cox"==t.regressionType&&(n.timeToEvent={timeId:t.outcome.id+"_time",eventId:t.outcome.id+"_event",timeScale:t.outcome.q.timeScale},"age"==n.timeToEvent.timeScale&&(n.timeToEvent.agestartId=t.outcome.id+"_agestart",n.timeToEvent.ageendId=t.outcome.id+"_ageend"));const r=[];for(const e of t.independent)"snplst"==e.type||"snplocus"==e.type?x(e,r,t):w(e,r,t);const o=[];for(const i of e){const{sample:e,id2value:s}=i;if(!s.has(t.outcome.id)){i.noOutcome=!0;continue}const a=s.get(t.outcome.id);let l=!1;for(const e of t.independent)if("snplocus"!=e.type)if("snplst"==e.type){for(const t of e.highAFsnps.keys())if(!s.get(t)){l=!0;break}}else{if(!s.get(e.id)){l=!0;break}}if(l)continue;const c={};if("linear"==t.regressionType&&(c[n.id]=a.value),"logistic"==t.regressionType&&(c[n.id]=a.key===t.outcome.refGrp?0:1),"cox"==t.regressionType){c[n.timeToEvent.eventId]=a.key;const{age_start:e,age_end:r}=a.value;c[n.timeToEvent.timeId]=r-e,"age"==t.outcome.q.timeScale&&(c[n.timeToEvent.agestartId]=e,c[n.timeToEvent.ageendId]=r)}for(const t of r){const e=s.get(t.id);c[t.id]=e?"numeric"===t.rtype?e.value:e.key:null}o.push(c)}const i={regressionType:t.regressionType,binpath:c.binpath,data:o,outcome:n,independent:r};return i}(t,n);y=(new Date).getTime(),v.NodeJS.makeRinput=(y-g)/1e3+" sec",function(t){const e=t.regressionType,n=t.outcome;if(t.data.length<m)throw"too few samples to fit model";let r=t.independent.length;if("cox"==e)if("time"==n.timeToEvent.timeScale)r+=2;else{if("age"!=n.timeToEvent.timeScale)throw"unknown cox regression time scale";r+=4}else r+=1;if(t.data.find((t=>Object.keys(t).length!=r)))throw"unequal number of variables in data entries";if("logistic"==e){if([...new Set(t.data.map((t=>t[n.id])))].find((t=>![0,1].includes(t))))throw"non-0/1 outcome values found"}if("cox"==e){if([...new Set(t.data.map((t=>t[n.timeToEvent.eventId])))].find((t=>![0,1].includes(t))))throw"non-0/1 outcome event values found"}for(const e of t.independent)if("numeric"==e.rtype){if(e.refGrp)throw`reference group given for '${e.id}'`}else{if("factor"!=e.rtype)throw`variable rtype='${e.rtype}' not recognized`;{if(!e.refGrp)throw`reference group not given for '${e.id}'`;if("snplst"==e.type||"snplocus"==e.type)continue;const n=new Set(t.data.map((t=>t[e.id])));if(n.size<2)throw`fewer than 2 categories in data of variable='${e.id}'`;if(!n.has(e.refGrp))throw`reference group missing in data of variable='${e.id}'`}}}(r);const[s,a]=function(t){const e={},n={};if(e.outcome=t.outcome.id,n[t.outcome.id]="outcome",t.outcome.timeToEvent){const r=t.outcome.timeToEvent;e.outcome_time=r.timeId,n[r.timeId]="outcome_time",e.outcome_event=r.eventId,n[r.eventId]="outcome_event","age"==r.timeScale&&(e.outcome_agestart=r.agestartId,e.outcome_ageend=r.ageendId,n[r.agestartId]="outcome_agestart",n[r.ageendId]="outcome_ageend")}for(const[r,o]of t.independent.entries())e["id"+r+"_"]=o.id,n[o.id]="id"+r+"_";if(t.outcome.id=n[t.outcome.id],t.outcome.timeToEvent){const e=t.outcome.timeToEvent;e.timeId=n[e.timeId],e.eventId=n[e.eventId],"age"==e.timeScale&&(e.agestartId=n[e.agestartId],e.ageendId=n[e.ageendId])}for(const e of t.independent)if(e.id=n[e.id],e.interactions&&e.interactions.length>0)for(const[t,r]of e.interactions.entries())e.interactions[t]=n[r];for(const e of t.data)for(const t in e)e[n[t]]=e[t],delete e[t];return[e,n]}(r),l={resultLst:[]};return await Promise.all([q(r,s,t,l),N(t,n,r,l)]),console.log("benchmark:",v),l}catch(t){return t.stack&&console.log(t.stack),{error:t.message||t}}}function _(t,e,n){if(!t.q.restrictAncestry)return;if(!("name"in t.q.restrictAncestry))throw".name missing from tw.q.restrictAncestry";if(!n.cohort.termdb.restrictAncestries)throw"ds.cohort.termdb.restrictAncestries missing";const r=n.cohort.termdb.restrictAncestries.find((e=>e.name==t.q.restrictAncestry.name));if(!r)throw"unknown ancestry for restriction: "+t.q.restrictAncestry.name;if(r.pcs)t.q.restrictAncestry.pcs=r.pcs;else{if(!r.PCfileBySubcohort)throw"unknown way of accessing pcs from ds.cohort.termdb.restrictAncestries: "+t.q.restrictAncestry.name;{if(!e.filter)throw"q.filter missing while trying to access subcohort for PCfileBySubcohort";const n=C(e.filter,"cohortFilter");if(!n)throw"tvs by tag=cohortFilter missing from q.filter.lst[] while trying to access subcohort for PCfileBySubcohort";const o=n.tvs.values.map((t=>t.key)).sort().join(","),i=r.PCfileBySubcohort[o];if(!i)throw"unknown key for PCfileBySubcohort: "+o;if(!i.pcs)throw"pcs Map() missing from PCfileBySubcohort[]: "+o;t.q.restrictAncestry.pcs=i.pcs}}}function w(t,e,n){const o={id:t.id,name:t.term.name,type:"spline"==t.q.mode?"spline":"other",rtype:"continuous"==t.q.mode||"spline"==t.q.mode?"numeric":"factor"};if(t.interactions.length>0){o.interactions=[];for(const e of t.interactions){const t=n.independent.find((t=>t.id==e));if("snplst"==t.type)for(const e of t.highAFsnps.keys())o.interactions.push(e);else{if("snplocus"==t.type)continue;o.interactions.push(e)}}}"factor"===o.rtype&&(o.refGrp=t.refGrp),"spline"==t.q.mode&&(o.spline={knots:t.q.knots.map((t=>Number(t.value)))},n.independent.find((t=>"snplocus"==t.type))||(o.spline.plotfile=r.join(c.cachedir,Math.random().toString()+".png"))),e.push(o)}function x(t,e,n){for(const r of t.highAFsnps.keys()){const o={id:r,name:r,type:t.type};3==t.q.geneticModel?(o.rtype="factor",o.refGrp=t.q.snp2refGrp[r]):o.rtype="numeric";for(const e of n.independent)e.interactions.includes(t.id)&&(o.interactions||(o.interactions=[]),o.interactions.push(e.id));e.push(o)}if(t.q.restrictAncestry)for(const n of t.q.restrictAncestry.pcs.keys())e.push({id:n,name:n,type:"float",rtype:"numeric"})}function k(t){if("condition"==t.term.type){for(const e of t.q.groups)if(e.name!=t.refGrp)return e;throw"nonref group not found for logistic outcome"}if("predefined-groupset"==t.q.type){if(!t.q.groupsetting)throw"outcome.q.groupsetting{} missing when type=predefined-groupset";if(!Number.isInteger(t.q.groupsetting.predefined_groupset_idx))throw'outcome.q.predefined_groupset_idx not integer when q.type is "predefined-groupset"';if(!t.term.groupsetting)throw"outcome.term.groupsetting missing";const e=t.term.groupsetting.lst[t.q.groupsetting.predefined_groupset_idx];if(!e)throw"groupset not found by outcome.q.predefined_groupset_idx";const n=e.groups.find((e=>e.name!=t.refGrp));if(!n)throw"non-ref group not found for predefined-groupset";return n.name}if("custom-groupset"==t.q.type){if(!t.q.groupsetting)throw"outcome.q.groupsetting{} missing when type=predefined-groupset";if(!t.q.groupsetting.customset)throw"outcome.q.customset missing";const e=t.q.groupsetting.customset.groups.find((e=>e.name!=t.refGrp));if(!e)throw"non-ref group not found for custom-groupset";return e.name}if("values"==t.q.type){if(!t.term.values)throw"outcome.term.values{} missing";for(const e in t.term.values){const n=t.term.values[e];if(n.label!=t.refGrp)return n.label}throw"unknown nonref group from outcome.term.values"}if("custom-bin"==t.q.type){const e=t.q.lst.find((e=>e.label!=t.refGrp));if(!e)throw"non-ref bin is not found for custom-bin";return e.label}if("regular-bin"==t.q.type)throw"do not know a way to find computed bin list for type=regular-bin";throw"unknown outcome.q.type"}async function q(t,e,n,o){g=(new Date).getTime();const i=r.join(c.cachedir,Math.random().toString()+".json");await u.write_file(i,JSON.stringify(t));const f=await s(r.join(c.binpath,"utils","regression.R"),[],[i]);a.unlink(i,(()=>{})),await async function(t,e,n,r,o){if(1!=e.length)throw"expected 1 json line in R output";const i=JSON.parse(e[0]),s=i.data;v["regression.R"]=i.benchmark;for(const e of s){const i={data:{sampleSize:e.data.sampleSize,eventCnt:e.data.eventCnt?e.data.eventCnt:null}};if(e.id){const t=n[e.id];i.id=t;const o=r.independent.find((t=>"snplocus"==t.type));if(!o)throw"snplocus term missing";i.AFstr=o.snpid2AFstr.get(t),i.data.headerRow=S(t,o)}const s=e.data;if(s.residuals&&(i.data.residuals=s.residuals,i.data.residuals.label="linear"==t.regressionType?"Residuals":"Deviance residuals"),"cox"==t.regressionType){if(s.coefficients.rows.length<1)throw"fewer than 1 row in coefficients table"}else if(s.coefficients.rows.length<2)throw"fewer than 2 rows in coefficients table";i.data.coefficients={header:s.coefficients.header,intercept:"cox"==t.regressionType?null:s.coefficients.rows.shift(),terms:{},interactions:[]};for(const t of s.coefficients.rows)if(-1!=t[0].indexOf(":")){const e={},[r,o]=t.shift().split(":"),[s,a]=t.shift().split(":");e.term1=n[r],e.category1=s,e.term2=n[o],e.category2=a,e.lst=t,i.data.coefficients.interactions.push(e)}else{const e=t.shift(),r=t.shift(),o=n[e];i.data.coefficients.terms[o]||(i.data.coefficients.terms[o]={}),r?(i.data.coefficients.terms[o].categories||(i.data.coefficients.terms[o].categories={}),i.data.coefficients.terms[o].categories[r]=t):i.data.coefficients.terms[o].fields=t}i.data.coefficients.label="Coefficients",i.data.type3={header:s.type3.header,terms:{},interactions:[]},"cox"!=t.regressionType&&(i.data.type3.intercept=s.type3.rows.shift());for(const t of s.type3.rows)if(-1!=t[0].indexOf(":")){const e={},[r,o]=t.shift().split(":");e.term1=n[r],e.term2=n[o],e.lst=t,i.data.type3.interactions.push(e)}else{const e=n[t.shift()];i.data.type3.terms[e]||(i.data.type3.terms[e]=t)}if(i.data.type3.label="Type III 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Buffer.from(n).toString("base64"),size:l(t)}),a.unlink(t,(t=>{if(t)throw t}))}s.warnings&&(i.data.warnings=s.warnings);const c=r.independent.find((t=>"snplst"==t.type));if(c){if(c.lowAFsnps&&c.lowAFsnps.size){i.data.warnings||(i.data.warnings=[]);for(const t of c.lowAFsnps.keys())i.data.warnings.push(`${t}: effect allele frequency below cutoff, excluded from analysis`)}if(c.monomorphicLst&&c.monomorphicLst.length){i.data.warnings||(i.data.warnings=[]);for(const t of c.monomorphicLst)i.data.warnings.push(`${t}: monomorphic, excluded from analysis`)}}o.resultLst.push(i)}}(t,f,e,n,o),y=(new Date).getTime(),v.NodeJS.runRegression=(y-g)/1e3+" sec"}async function N(t,e,n,o){const i=t.independent.find((t=>"snplocus"==t.type));if(i){if(g=(new Date).getTime(),function(t,e){for(const n of t.monomorphicLst){const r=t.snpgt2count.get(n),o=[];for(const[t,e]of r)o.push(t+"="+e);const i={id:n,data:{headerRow:S(n,t)}};e.resultLst.push(i)}}(i,o),i.lowAFsnps.size)if("linear"==t.regressionType)await async function(t,e,n,o){const i={},l=new Map;for(const[r,o]of t.lowAFsnps){let t=0,s=null,a=null;const c=[],u=[];for(const{sample:r,noOutcome:i}of e){if(i)continue;const e=n.data[t++].outcome;if(!Number.isFinite(e))continue;const l=o.samples.get(r);if(!l)continue;null==s?s=a=e:(s=Math.min(s,e),a=Math.max(a,e));const[f,d]=l.split("/");f==o.effAle||d==o.effAle?c.push(e):u.push(e)}i[r]={group1values:c,group2values:u},l.set(r,{minv:s,maxv:a})}const f=r.join(c.cachedir,Math.random().toString()+".json");await u.write_file(f,JSON.stringify(i));const d=await s(r.join(c.binpath,"utils/wilcoxon.R"),[],[f]);a.unlink(f,(()=>{}));const p=JSON.parse(d);for(const e in p){const{group1values:n,group2values:r}=i[e],{minv:s,maxv:a}=l.get(e),c=h.boxplot_getvalue(n.sort(((t,e)=>t-e)).map((t=>({value:t}))));c.label=`Carry ${0==t.q.alleleType?"minor":"alternative"} allele, n=${n.length}`;const u=h.boxplot_getvalue(r.sort(((t,e)=>t-e)).map((t=>({value:t}))));u.label=`No 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t.lowAFsnps){if(i.has(e)){a={pvalue:"NA",msg:"Cannot perform cumulative incidence test on this snp - at least one allele is not found in any sample"}}else{const t=[];for(const n of s.case)n[0]==e&&t.push(n);if(!s.tests[e]||!s.tests[e].length)throw"no tests for snp";const n=Number(s.tests[e][0].pvalue);if(!Number.isFinite(n))throw"invalid pvalue";const r={};r[e]=s.tests[e],a={pvalue:Number(n.toFixed(4)),final_data:{case:t,tests:r}}}const n={id:e,AFstr:t.snpid2AFstr.get(e),data:{headerRow:S(e,t),cuminc:a}};r.resultLst.push(n)}}(i,e,n,o)}y=(new Date).getTime(),v.NodeJS.snplocusPostprocess=(y-g)/1e3+" sec"}}function S(t,e){const n=e.snpgt2count.get(t);if(!n)return{k:"Error",v:"Variant not found"};if(e.monomorphicLst.includes(t)){const[t,e]=[...n][0];return{k:"Genotype",v:t+"="+e}}const r=[`${0==e.q.alleleType?"Minor":"Alternative"} allele=${e.highAFsnps.has(t)?e.highAFsnps.get(t).effAle:e.lowAFsnps.get(t).effAle}`,"AF="+e.snpid2AFstr.get(t)];for(const[t,e]of n)r.push(t+"="+e);return{k:"Variant:",v:r.join("&nbsp;&nbsp;&nbsp;")}}function A(t,e,n){if(t.q.restrictAncestry)for(const[n,r]of t.q.restrictAncestry.pcs)for(const[t,o]of r)e.has(t)&&e.get(t).id2value.set(n,{key:o,value:o})}async function M(t,e,n){const o=(await u.read_file(r.join(c.cache_snpgt.dir,t.q.cacheid))).split("\n"),i=o[0].split("\t").slice(c.cache_snpgt.sampleColumn).map(Number);if(n)for(const t of i)e.set(t,{id2value:new Map});const s=i.map((t=>e.has(t))),a=new Map;for(let e=1;e<o.length;e++){const n=o[e].split("\t"),r=n[0],l={refAle:n[3],altAles:n[4].split(","),samples:new Map};t.q.snp2effAle?l.effAle=t.q.snp2effAle[r]:l.effAle=l.altAles[0],a.set(r,l);for(const[t,e]of i.entries()){if(!s[t])continue;const o=n[t+c.cache_snpgt.sampleColumn];o&&a.get(r).samples.set(e,o)}}"snplocus"!=t.type&&function(t,e,n,r){if(0==e.q.missingGenotype){for(const e of t.values()){let t;if(e.refAle!=e.effAle)t=e.refAle;else for(const n of e.altAles)if(n!=e.effAle){t=n;break}if(!t)throw"not finding 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connect db ${e}: ${t.message||t}`}t.cohort.db.connection=n;const r=l(n);if(!r.has("terms"))throw"terms table missing";if(!r.has("ancestry"))throw"ancestry table missing";if(t.cohort.termdb.selectCohort&&!r.has("subcohort_terms"))throw"subcohort_terms table is missing while termdb.selectCohort is enabled";t.cohort.termdb.q={};const a=t.cohort.termdb.q;if(r.has("buildDate")&&(a.get_buildDate=n.prepare("select date from buildDate")),r.has("term2genes")){t.cohort.termdb.termMatch2geneSet=!0;const e=n.prepare("SELECT genes FROM term2genes WHERE id=?"),r=new Map;a.getGenesetByTermId=t=>{if(r.has(t))return r.get(t);const n=e.get(t);if(n&&n.genes){const e=JSON.parse(n.genes);return r.set(t,e),e}}}if(r.has("sampleidmap")){const e=new Map,r=new Map,o=n.prepare("SELECT * FROM sampleidmap");let i=0;for(const{id:t,name:n}of o.all())e.set(t,n),r.set(n,t),i++;if(a.id2sampleName=t=>e.get(t),a.sampleName2id=t=>r.get(t),t.cohort.termdb.selectCohort){const t=n.prepare("SELECT cohort,sample_count from 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o&&o.id&&(r=!1),e.set(n,r),r}}{const t=n.prepare("SELECT id, name, jsondata, s.included_types, s.child_types\n\t\t\tFROM terms t\n\t\t\tJOIN subcohort_terms s ON s.term_id = t.id AND s.cohort=?\n\t\t\tWHERE parent_id is null\n\t\t\tGROUP BY id\n\t\t\tORDER BY child_order ASC"),e=new Map;a.getRootTerms=(n="")=>{const r=n;if(e.has(r))return e.get(r);const o=t.all(n).map((t=>{const e=JSON.parse(t.jsondata);return e.id=t.id,e.name=t.name||e.name,e.included_types=t.included_types?t.included_types.split(","):["TO-DO-PLACEHOLDER"],e.child_types=t.child_types?t.child_types.split(","):[],e}));return e.set(r,o),o}}{const t=n.prepare("SELECT parent_id FROM terms WHERE id=?");{const e=new Map;a.termHasParent=n=>{if(e.has(n))return e.get(n);let r=!1;const o=t.get(n);return o&&o.parent_id&&(r=!0),e.set(n,r),r}}{const e=new Map;a.getTermParentId=n=>{if(e.has(n))return e.get(n);let r;const o=t.get(n);return o&&o.parent_id&&(r=o.parent_id),e.set(n,r),r}}{const t=new Map;a.getTermParent=e=>{if(t.has(e))return t.get(e);const n=a.getTermParentId(e);let r;return n&&(r=a.termjsonByOneid(n)),t.set(e,r),r}}}{const t=n.prepare("SELECT id, name, type, jsondata, s.included_types, s.child_types \n\t\t\tFROM terms t\n\t\t\tJOIN subcohort_terms s ON s.term_id = t.id AND s.cohort=? \n\t\t\tWHERE id IN (SELECT id FROM terms WHERE parent_id=?)\n\t\t\tGROUP BY id\n\t\t\tORDER BY child_order ASC"),e=new Map;a.getTermChildren=(n,r="")=>{const o=n+";;"+r;if(e.has(o))return e.get(o);const i=t.all([r,n]);let s;return i&&(s=i.map((t=>{const e=JSON.parse(t.jsondata);return e.id=t.id,e.name=t.name||e.name,e.included_types=t.included_types?t.included_types.split(","):[],e.child_types=t.child_types?t.child_types.split(","):[],e}))),e.set(o,s),s}}{const t=n.prepare("SELECT id, name, jsondata, s.included_types\n\t\t\tFROM terms t\n\t\t\tJOIN subcohort_terms s ON s.term_id = t.id AND s.cohort=?\n\t\t\tWHERE name LIKE ?");a.findTermByName=(e,n=10,r="",o=null,i=null,a=null)=>{const l=t.all([r,"%"+e+"%"]);if(l){const t=a||{equals:[],startsWith:[],startsWord:[],includes:[]};for(const n of l){if(!n.jsondata)continue;const r=n.name.toLowerCase(),o=JSON.parse(n.jsondata);o.id=n.id,o.name=n.name||o.name,o.included_types=n.included_types?n.included_types.split(","):[],i&&!(0,s.CG)(o,i).has("plot")||(r===e?t.equals.push(o):r.startsWith(e)?t.startsWith.push(o):r.includes(" "+e)?t.startsWord.push(o):t.includes.push(o))}return[...t.equals,...t.startsWith,...t.startsWord,...t.includes].slice(0,n)}}}{const t=n.prepare("SELECT MAX(value) AS v FROM anno_integer WHERE term_id=?"),e=n.prepare("SELECT MAX(value) AS v FROM anno_float WHERE term_id=?"),r=new Map;a.findTermMaxvalue=(n,o)=>{if(r.has(n))return r.get(n);const i=(o?t:e).get(n);return i?(r.set(n,i.v),i.v):void 0}}{const t=n.prepare("SELECT ancestor_id FROM ancestry WHERE term_id=?"),e=new Map;a.getAncestorIDs=n=>{if(e.has(n))return e.get(n);const r=t.all(n).map((t=>t.ancestor_id));return e.set(n,r),r}}{const t=n.prepare("SELECT t.name FROM ancestry as a, terms as t WHERE a.term_id=? AND t.id=a.ancestor_id"),e=new Map;a.getAncestorNames=n=>{if(e.has(n))return e.get(n);const r=t.all(n).map((t=>t.name));return e.set(n,r),r}}{const t={categorical:n.prepare("SELECT value FROM anno_categorical WHERE term_id=?"),integer:n.prepare("SELECT value FROM anno_integer WHERE term_id=?"),float:n.prepare("SELECT value FROM anno_float WHERE term_id=?")},e={categorical:n.prepare("SELECT value FROM anno_categorical WHERE term_id=? AND sample=?"),integer:n.prepare("SELECT value FROM anno_integer WHERE term_id=? AND sample=?"),float:n.prepare("SELECT value FROM anno_float WHERE term_id=? AND sample=?")},r={categorical:n.prepare("SELECT value FROM anno_categorical a,sampleidmap s WHERE term_id=? AND s.name=?"),integer:n.prepare("SELECT value FROM anno_integer a,sampleidmap s WHERE term_id=? AND s.name=?"),float:n.prepare("SELECT value FROM anno_float a, sampleidmap s WHERE term_id=? AND s.name=?")};a.getSample2value=(n,o=null)=>{const i=a.termjsonByOneid(n);return o?"string"==typeof o?r[i.type].all(n,o):e[i.type].all(n,o):t[i.type].all(n)}}if(r.has("termhtmldef")){const t=n.prepare("SELECT jsonhtml FROM termhtmldef WHERE id=?"),e=new Map;a.getTermInfo=n=>{if(e.has(n))return e.get(n);const r=t.get(n);if(r){const t=JSON.parse(r.jsonhtml);return t.id=n,e.set(n,t),t}}}a.getSupportedChartTypes=e=>{var n;c(t);const r=null===(n=o().dsCredentials)||void 0===n?void 0:n[t.label],i={},s={};for(const n of t.cohort.termdb.termtypeByCohort){var a;if(n.type){var l,u;if(!(n.cohort in i))i[n.cohort]=new Set(["regression","summary"]),t.cohort.scatterplots&&i[n.cohort].add("sampleScatter"),s[n.cohort]=0,null!==(l=t.cohort.allowedChartTypes)&&void 0!==l&&l.includes("matrix")&&i[n.cohort].add("matrix"),(!r||null!==(u=r.embedders)&&void 0!==u&&u[e])&&i[n.cohort].add("dataDownload");null!==(a=o().features)&&void 0!==a&&a.draftChartTypes&&i[n.cohort].add(...o().features.draftChartTypes),"survival"!=n.type||i[n.cohort].has("survival")||i[n.cohort].add("survival"),"condition"!=n.type||i[n.cohort].has("cuminc")||i[n.cohort].add("cuminc"),"float"!=n.type&&"integer"!=n.type||(s[n.cohort]+=n.samplecount)}}for(const t in s)s[t]>1&&i[t].add("sampleScatter");for(const t in i)i[t]=[...i[t]];if(t.cohort.allowedChartTypes)for(const e in i)i[e]=i[e].filter((e=>t.cohort.allowedChartTypes.includes(e)));if(t.queries){if(t.queries.snvindel||t.queries.trackLst)for(const t in i)i[t].push("genomeBrowser");if(t.queries.geneExpression)for(const t in i)i[t].push("geneExpression")}return i}}function l(t){const e=t.prepare("SELECT name FROM sqlite_master WHERE type='table'").all();return new Set(e.map((t=>t.name)))}function c(t){var e,n;if(t.cohort.termdb.termtypeByCohort){if(!Array.isArray(t.cohort.termdb.termtypeByCohort))throw"termtypeByCohort is not array"}else{if(null===(e=t.cohort)||void 0===e||null===(n=e.db)||void 0===n||!n.connection)throw"termtypeByCohort[] not set but cohort.db.connection missing";t.cohort.termdb.termtypeByCohort=t.cohort.db.connection.prepare("WITH c AS (\n\t\t\tSELECT cohort, term_id\n\t\t\tFROM subcohort_terms s\n\t\t\tGROUP BY cohort, term_id\n\t\t) \n\t\tSELECT cohort, type, count(*) as samplecount\n\t\tFROM terms t\n\t\tJOIN c ON c.term_id = t.id\n\t\tGROUP BY cohort, type").all()}}},3795:(t,e,n)=>{"use strict";n.r(e),n.d(e,{add_bcf_variant_filter:()=>p,validate:()=>h});const r=n(7147),o=n(1017),i=n(3856),s=n(2852),a=(n(7860),n(4521),n(334)),{compute_mclass:l}=n(3625),c="%CHROM\t%POS\t%REF\t%ALT[\t%TGT]\n",u="%POS\t%ID\t%REF\t%ALT\t%INFO[\t%TGT]\n",f=".",d=1e3;async function h(t,e,n,h){try{if(t.sumSamples)return await async function(t,e,n,r){if(!t.cacheid)throw"cacheid missing";if(a.cache_snpgt.fileNameRegexp.test(t.cacheid))throw"invalid cacheid";let l,c;if(n.track){if(l=n.track.vcf,!l)throw"ds.track.vcf missing"}else l=n.queries.snvindel.byrange._tk;if(t.filter){const e=new Set((await s.get_samples(t.filter,n)).map((t=>t.id)));if(0==e.size)throw"no samples from filter";c=l.samples.map((t=>e.has(t.name)))}else c=l.samples.map((t=>!0));const u=(await i.read_file(o.join(a.cache_snpgt.dir,t.cacheid))).split("\n"),f=new Set,d=[];for(let t=1;t<u.length;t++){const e=u[t].split("\t"),n=e[0],r=e[3],o={},i={};for(let t=a.cache_snpgt.sampleColumn;t<e.length;t++){const n=e[t];if(!n)continue;if(!c[t-a.cache_snpgt.sampleColumn])continue;f.add(l.samples[t-a.cache_snpgt.sampleColumn].name),i[n]=1+(i[n]||0);const r=n.split("/");for(const t of r)o[t]=1+(o[t]||0)}const s=[];for(const t in o)s.push({allele:t,count:o[t],isRef:t==r});d.push({snpid:n,alleles:s,gt2count:i})}return{numOfSampleWithAnyValidGT:f.size,snps:d}}(t,0,n);if(t.snptext)return await async function(t,e,n){if(!n.snp)throw"snp not supported by genome";if(!t.snptext)throw".snptext missing";const s=function(t){const e=[];for(const n of t.trim().split("\n")){const[t,r]=n.trim().split(/[\s\t]/);if(t&&t.startsWith("rs")){if(e.find((e=>e.rsid==t)))continue;const n={rsid:t,snpid:t};r&&(n.effectAllele=r),e.push(n)}else e.push({rsid:t,snpid:t,invalid:"INVALID RSID"})}return e}(t.snptext);if(!s.length)throw"no snps";await async function(t,e){for(const n of t)if(!n.invalid)if(n.chr&&"string"==typeof n.chr){const t=e.chrlookup[n.chr.toUpperCase()];if(!t){n.invalid=!0;continue}if(!Number.isInteger(n.pos)){n.invalid=!0;continue}if(n.pos<=0||n.pos>=t.len){n.invalid=!0;continue}}else if(n.rsid){const t=await i.query_bigbed_by_name(e.snp.bigbedfile,n.rsid),r=[];for(const n of t){const t=n.split("\t"),o=e.chrlookup[t[0].toUpperCase()];o&&o.major&&r.push(t)}if(0==r.length){n.invalid=!0;continue}const o=r[0];n.chr=o[0],n.pos=Number.parseInt(o[1]),n.dbsnpRef=o[4],n.dbsnpAlts=o[6].split(",").filter(Boolean)}else n.invalid=!0;if(!t.find((t=>!t.invalid)))throw"no valid variants"}(s,n);const l=await async function(t,e,n){let s;if(n.track){if(s=n.track.vcf,!s)throw"ds.track.vcf missing"}else s=n.queries.snvindel.byrange._tk;const l=new Set,u=[];for(const t of e){if(t.invalid)continue;let e;var d;if(s.chr2files){if(e=null===(d=s.chr2files)||void 0===d?void 0:d[t.chr].file,!e)throw"chr not in chr2files"}else if(s.chr2bcffile){if(e=s.chr2bcffile[t.chr],!e)throw"chr not in chr2bcffile"}else e=s.file||s.url;l.add(e);const n=(s.nochr?t.chr.replace("chr",""):t.chr)+"\t"+(t.pos+1);u.push(n)}const h=o.join(a.cachedir,await i.write_tmpfile(u.join("\n"))),p=o.join(a.cachedir,await i.write_tmpfile([...l].join("\n")));await i.get_lines_bigfile({isbcf:!0,args:["query","-R",h,"-f",c,"-v",p],dir:s.dir,callback:t=>{const n=t.split("\t"),r=(s.nochr?"chr":"")+n[0],o=n[1],i=n[2],a=n[3].split(","),l=e.find((t=>{if(t.chr==r&&t.pos===o-1&&t.dbsnpRef==i&&t.dbsnpAlts.some((t=>a.includes(t))))return t}));if(l){l.referenceAllele=i,l.altAlleles=a,l.gtlst=[];for(let t=4;t<n.length;t++)l.gtlst.push(n[t]==f?"":n[t])}}}),r.unlink(h,(()=>{})),r.unlink(p,(()=>{}));const m=["snpid\tchr\tpos\tref\talt\teff\t"+s.samples.map((t=>t.name)).join("\t")];for(const t of e)t.invalid||t.gtlst&&(m.push(t.snpid+"\t"+t.chr+"\t"+t.pos+"\t"+t.referenceAllele+"\t"+t.altAlleles.join(",")+"\t"+(t.effectAllele||"")+"\t"+t.gtlst.join("\t")),delete t.gtlst);const g=t.genome+"_"+t.dslabel+"_"+new Date/1+"_"+Math.ceil(1e4*Math.random());return await i.write_file(o.join(a.cache_snpgt.dir,g),m.join("\n")),g}(t,s,e);return{snps:s,cacheid:l}}(t,n,h);if(t.chr)return await async function(t,e,n){const r=Number(t.start),s=Number(t.stop);if(!Number.isInteger(r)||!Number.isInteger(s))throw"start/stop are not integers";if(r>s||r<0)throw"invalid start/stop coordinate";let c,h;if(e.track){if(c=e.track.vcf,!c)throw"ds.track.vcf missing";if(h=c.chr2bcffile[t.chr],!h)throw"chr not in chr2bcffile"}else{var m;if(c=e.queries.snvindel.byrange._tk,c.chr2files)h=null===(m=c.chr2files)||void 0===m?void 0:m[t.chr].file;else h=c.file||c.url;if(!h)throw"no bcf file"}const g=(c.nochr?t.chr.replace("chr",""):t.chr)+":"+r+"-"+s,y=["query",h,"-r",g,"-f",u];t.variant_filter&&p(t.variant_filter,y);const v={snps:[]},b=["snpid\tchr\tpos\tref\talt\teff\t"+c.samples.map((t=>t.name)).join("\t")];return await i.get_lines_bigfile({isbcf:!0,args:y,dir:c.dir,callback:(e,n)=>{if(v.snps.length>=d)return n.kill(),void(v.reachedVariantLimit=!0);const r=e.split("\t"),o=Number(r[0])-1,i=r[2],s=r[3].split(","),a=o+"."+i+"."+s.join(","),u={snpid:a,chr:t.chr,pos:o};l(c,i,s,u,r[4],r[1]);for(const t of u.mlst)t.vcf_id&&(t.mname=t.vcf_id);v.snps.push(u);const h=[a,t.chr,o,i,s.join(","),""];for(let t=5;t<r.length;t++)h.push(r[t]==f?"":r[t]);b.push(h.join("\t"))}}),v.cacheid=t.genome+"_"+t.dslabel+"_"+new Date/1+"_"+Math.ceil(1e4*Math.random()),await i.write_file(o.join(a.cache_snpgt.dir,v.cacheid),b.join("\n")),v}(t,n);throw"unknown how to validate"}catch(t){return t.stack&&console.log(t.stack),{error:t.message||t}}}function p(t,e){const n=[];for(const e of t.lst)if(e.tvs.values){const t=e.tvs.isnot?"!=":"=";for(const r of e.tvs.values){const o=isNaN(r.key)?`"${r.key}"`:Number(r.key);n.push(`INFO/${e.tvs.term.id}${t}${o}`)}}else{if(!e.tvs.ranges)throw`unknown tvs spec for info_field: type=${e.type}, term.id=${e.tvs.term.id}`;for(const t of e.tvs.ranges)"start"in t&&n.push(`INFO/${e.tvs.term.id} ${t.startinclusive?">=":">"} ${t.start}`),"stop"in t&&n.push(`INFO/${e.tvs.term.id} ${t.stopinclusive?"<=":"<"} ${t.stop}`)}0!=n.length&&e.push("-i",n.join(" && "))}},2747:(t,e,n)=>{"use strict";n.r(e),n.d(e,{groupset:()=>s,values:()=>o});var r=n(2852);const o={getCTE(t,e,n,o,i){i.push(e.id);const s=(0,r.getUncomputableClause)(e,o);return i.push(...s.values),{sql:`${t} AS (\n\t\t\t\tSELECT sample,value as key, value as value\n\t\t\t\tFROM anno_categorical\n\t\t\t\tWHERE term_id=? ${s.clause}\n\t\t\t)`,tablename:t}}};let i=0;const s={async getCTE(t,e,n,r,o,s){if(!s.groups)throw`.groups[] missing from a group-set, term.id='${e.id}'`;const a=[],l=[];for(const t of s.groups)if("values"==t.type)a.push(`SELECT sample, ? as key, value\n\t\t\t\t\tFROM anno_categorical a\n\t\t\t\t\tWHERE term_id=?\n\t\t\t\t\t\tAND value IN (${t.values.map((t=>"?")).join(",")})\n\t\t\t\t`),o.push(t.name,e.id,...t.values.map((t=>t.key.toString())));else{if("filter"!=t.type)throw`unsupported groupset type='${t.type}'`;if(!("activeCohort"in r.groupsetting)||!t.filter4activeCohort)throw`activeCohort error: cannot construct filter statement for group name='${t.name}', term.id=${e.id}`;{const s=t.filter4activeCohort[r.groupsetting.activeCohort],c=await getFilterCTEs(s,n,"xf"+i++);if(!c)throw`unable to construct a group='${t.name}' filter for term.id='${e.id}'`;l.push(c.filters),o.push(...c.values.slice(),t.name,t.name),a.push(`SELECT sample, ? AS key, ? AS value\n\t\t\t\t\t\tFROM ${c.CTEname}`)}}return{sql:`${l.length?l.join("\n,")+",":""}\n\t\t\t${t} AS (\n\t\t\t\t${a.join("\nUNION ALL\n")}\n\t\t\t)`,tablename:t}}}},6759:(t,e,n)=>{"use strict";function r(t){const e=t.cohort.db.connection.prepare("select * from features").all();return{cohorts:t.cohort.db.connection.prepare("select * from cohorts where cohort in (select distinct(cohort) from cohort_features)\n\t\t order by sample_count desc").all(),features:e,cfeatures:t.cohort.db.connection.prepare("select * from cohort_features").all()}}n.r(e),n.d(e,{getCohortsData:()=>r})},9723:(t,e,n)=>{"use strict";n.r(e),n.d(e,{binary:()=>i,cox:()=>a,cuminc:()=>s,discrete:()=>o});var r=n(2852);const o={getCTE(t,e,n,o,i){if(o.breaks&&o.breaks.length>0)return c(t,e,o,i);{const[n,s]=l(o);i.push(e.id);const a=(0,r.getUncomputableClause)(e,o);return i.push(...a.values),{sql:`${t} AS (\n\t\t\t\t\tSELECT\n\t\t\t\t\t\tsample,\n\t\t\t\t\t\tvalue as key,\n\t\t\t\t\t\tvalue\n\t\t\t\t\tFROM\n\t\t\t\t\t\t${"grade"==n?"precomputed_chc_grade":"precomputed_chc_child"}\n\t\t\t\t\tWHERE\n\t\t\t\t\t\tterm_id = ?\n\t\t\t\t\t\tAND ${s} = 1\n\t\t\t\t\t\t${a.clause}\n\t\t\t\t)`,tablename:t}}}},i={getCTE(t,e,n,r,o){var i;if(1!=(null===(i=r.breaks)||void 0===i?void 0:i.length))throw"binary mode requires one break";return c(t,e,r,o)}},s={getCTE(t,e,n,r,o){var i;if(1!=(null===(i=r.breaks)||void 0===i?void 0:i.length))throw"cuminc mode requires one break";return o.push(e.id,r.breaks[0]),{sql:`${t} AS (\n\t\t\t\tSELECT\n\t\t\t\t\tsample,\n\t\t\t\t\tevent AS key,\n\t\t\t\t\ttime AS value\n\t\t\t\tFROM\n\t\t\t\t\tprecomputed_cuminc\n\t\t\t\tWHERE\n\t\t\t\t\tterm_id = ?\n\t\t\t\t\tAND grade_cutoff = ?\n\t\t\t)`,tablename:t}}},a={getCTE(t,e,n,r,o){var i;if(1!=(null===(i=r.breaks)||void 0===i?void 0:i.length))throw"cox mode requires one break";return o.push(e.id,r.breaks[0]),{sql:`${t} AS (\n\t\t\t\tSELECT\n\t\t\t\t\tsample,\n\t\t\t\t\tjson_object('event', event, 'label', IIF(event = 0, 'Censored', IIF(event = 1, 'Event (grade ${r.breaks[0]}-5)', IIF(event = -1, 'Event before entry into the cohort', 'NA')))) AS key,\n\t\t\t\t\tjson_object('age_start', age_start, 'age_end', age_end) AS value\n\t\t\t\tFROM\n\t\t\t\t\tprecomputed_cox\n\t\t\t\tWHERE\n\t\t\t\t\tterm_id = ?\n\t\t\t\t\tAND grade_cutoff = ?\n\t\t\t)`,tablename:t}}};function l(t){const e=t.bar_by_children?"child":t.bar_by_grade?"grade":"";if(!e)throw"must set the bar_by_grade or bar_by_children query parameter";const n=t.value_by_max_grade?"max_grade":t.value_by_most_recent?"most_recent":t.value_by_computable_grade?"computable_grade":"";if(!n)throw"must set a valid value_by_*";return[e,n]}function c(t,e,n,r){const[o,i]=l(n);if("grade"!=o)throw"breaks must be used on grade values";const s=[];for(const t of n.groups)s.push(`SELECT sample, ? as key, value\n\t\t\tFROM precomputed_chc_grade\n\t\t\tWHERE\n\t\t\t\tterm_id=?\n\t\t\t\tAND ${i}=1\n\t\t\t\tAND value IN (${t.values.map((t=>"?")).join(",")})\n\t\t`),r.push(t.name,e.id,...t.values.map((t=>t.toString())));return{sql:`${t} AS (\n\t\t\t${s.join("\nUNION ALL\n")}\n\t\t)`,tablename:t}}},2852:(t,e,n)=>{"use strict";n.r(e),n.d(e,{getUncomputableClause:()=>v,get_bins:()=>_,get_numericMinMaxPct:()=>x,get_numericsummary:()=>w,get_rows:()=>p,get_rows_by_one_key:()=>h,get_samplecount:()=>f,get_samples:()=>u,get_summary:()=>g,get_summary_numericcategories:()=>d,get_term_cte:()=>m,interpolateSqlValues:()=>k});const r=n(9699),o=n(4048),i=n(5257).getFilterCTEs,s=n(827),a=n(2747),l=n(9723),c=n(610).s;n(334);async function u(t,e,n=!1){const r=await i(t,e),o=e.cohort.db.connection.prepare(r?`WITH ${r.filters} SELECT sample as id, name FROM ${r.CTEname} join sampleidmap on sample = sampleidmap.id`:"SELECT id, name FROM sampleidmap");let s;if(s=r?o.all(r.values):o.all(),n)return s;for(const t of s)delete t.name;return s}async function f(t,e){if(!t.filter)throw"filter missing";let n;if("object"==typeof t.filter)n=t.filter;else{if("string"!=typeof t.filter)throw"q.filter not obj or str";n=JSON.parse(t.filter)}const r=await i(n,e),o=`WITH ${r.filters}\n\t\tSELECT 'FILTERED_COHORT' as subcohort, count(distinct sample) as samplecount \n\t\tFROM ${r.CTEname}`;return e.cohort.db.connection.prepare(o).all(r.values)}async function d(t){const e=t.ds.cohort.termdb.q.termjsonByOneid(t.term_id);if("integer"!=e.type&&"float"!=e.type)throw"term is not numeric";if(!e.values)return[];const n=await i(t.filter,t.ds),r=n?n.values.slice():[];r.push(t.term_id);const o=[];for(const t in e.values)o.push("?"),r.push(Number(t));const s=`\n\t\t${n?"WITH "+n.filters:""}\n\t\tSELECT count(sample) AS samplecount,value\n\t\tFROM anno_${e.type}\n\t\tWHERE term_id=?\n\t\t${n?"AND sample IN "+n.CTEname:""}\n\t\tAND value IN (${o.join(",")})\n\t\tGROUP BY value`;return t.ds.cohort.db.connection.prepare(s).all(r)}async function h(t){if(!t.key)throw".key missing";if(!t.ds)throw".ds{} missing";const e=await i(t.filter,t.ds),n=e?e.values.slice():[],r=t.ds.cohort.termdb.q.termjsonByOneid(t.key);n.push(t.key);const o=`\n\t\t${e?"WITH "+e.filters:""}\n\t\tSELECT sample, value\n\t\tFROM anno_${r.type}\n\t\tWHERE term_id=?\n\t\t${e?" AND sample IN "+e.CTEname:""}`;return t.ds.cohort.db.connection.prepare(o).all(n)}async function p(t,e={}){"string"==typeof t.filter&&(t.filter=JSON.parse(decodeURIComponent(t.filter)));const n=Object.assign({withCTEs:!0,columnas:"t1.sample AS sample",groupby:""},e),r=await i(t.filter,t.ds),o=r?r.values.slice():[],s=await m(t,o,0,r),a=await m(t,o,1,r),l=await m(t,o,2,r),c=[s,a,l].map(((t,e)=>`\n\t\tSELECT sample, key, value, ${e} as termNum\n\t\tFROM ${t.tablename}\n\t\t${r?"WHERE sample IN "+r.CTEname:""}\n\t`)).join("\nUNION ALL\n"),u=`WITH\n\t\t${r?r.filters+",":""}\n\t\t${s.sql},\n\t\t${a.sql},\n\t\t${l.sql}\n\t\t${c}`;try{const e=t.ds.cohort.db.connection.prepare(u).all(o),i=new Map;for(const t of e){i.has(t.sample)||i.set(t.sample,{sample:t.sample});const e=i.get(t.sample),n=`key${t.termNum}`;n in e||(e[n]=[]),e[n].push(t)}const c=[],f=new Map;for(const e of i.values())if("key1"in e){if(t.term0_q&&t.term0_id){if(!("key0"in e))continue}else e.key0=[{key:"",value:""}];if(t.term2_q&&(t.term2_id||"samplelst"===t.term2.type)){if(!("key2"in e))continue}else e.key2=[{key:"",value:""}];e.rows=[];for(const t of e.key0)for(const n of e.key1)for(const r of e.key2)e.rows.push({sample:e.sample,key0:t.key,val0:t.value,key1:n.key,val1:n.value,key2:r.key,val2:r.value});for(const t of e.rows)if(n.groupby){if(!f.has(t[n.groupby])){const e=Object.assign({samplecount:0},t);c.push(e),f.set(t[n.groupby],e)}f.get(t[n.groupby]).samplecount++}else c.push(t)}return n.withCTEs?{lst:c,CTE0:s,CTE1:a,CTE2:l,filter:r}:c}catch(t){throw console.log("error in sql:\n",k(u,o)),t}}async function m(t,e,n,r,o=null){const i=o&&o.term||t[`term${n}`],u=i?i.id:t["term"+n+"_id"];if("samplelst"!=(null==i?void 0:i.type))if(o||1!=n){if(!u){const t="samplekey_"+n;return{tablename:t,sql:`${t} AS (\nSELECT null AS sample, '' as key, '' as value\n)`}}}else if(!u)throw"missing term1 id";const f=i&&i.type?i:t.ds.cohort.termdb.q.termjsonByOneid(u);if(!f)throw`no term found by id='${u}'`;let d=o&&o.q||t["term"+n+"_q"]||{};"string"==typeof d&&(d=JSON.parse(decodeURIComponent(d)));const h="samplekey_"+n;let p;if("categorical"==f.type){const n=b(f,d);p=await a[n?"groupset":"values"].getCTE(h,f,t.ds,d,e,n)}else if("integer"==f.type||"float"==f.type){const o="spline"==d.mode?"cubicSpline":d.mode||"discrete";p=await s[o].getCTE(h,f,t.ds,d,e,n,r)}else if("condition"==f.type){const n=d.mode||"discrete";p=await l[n].getCTE(h,f,t.ds,d,e)}else if("survival"==f.type)p=function(t,e,n,r,o){return r.push(e.id),{sql:`${t} AS (\n\t\t\tSELECT sample, exit_code as key, tte AS value\n\t\t\tFROM survival s\n\t\t\tWHERE s.term_id=?\n\t\t\t${o?"AND s.sample IN "+o.CTEname:""}\n\t\t)`,tablename:t}}(h,f,0,e,r);else{if("samplelst"!=f.type)throw"unknown term type";p=await c.getCTE(h,o||{term:f,q:d},e)}return p}async function g(t){const e=await p(t,{withCTEs:!0,groupby:"key1"}),n=[0,1,2],r={};for(const o of n)r[o]=y(t,o,e);for(const t of e.lst)for(const e of n)r[e](t);return e}function y(t,e,n){const r="key"+e,o="val"+e,i=t=>{delete t[r],delete t[o]},s=t["term"+e+"_id"];if(!s)return i;const a=t.ds.cohort.termdb.q.termjsonByOneid(s);if(!a)return i;const l=1!=e||t.term0_id||t.term2_id?r:"key",c=1!=e||t.term0_id||t.term2_id?r:"label";if("integer"==a.type||"float"==a.type){const i=n["CTE"+e],s="range"+(1!=e||t.term0_id||t.term2_id?e:"");return t=>{t[s]=i.name2bin.get(t[r]),t[c]=t[r],delete t[o],l!==r&&(t[l]=t[r],delete t[r])}}{const n=t["term"+e+"_q"];return e=>{e[c]=function(t,e,n,r){if("categorical"==e.type)return e.values&&t in e.values?e.values[t].label:t;if("condition"==e.type){var o;if(0==(null===(o=n.breaks)||void 0===o?void 0:o.length)){if(!(t in e.values))throw`unknown grade='${t}'`;return e.values[t].label}return t}if(e.values)return t in e.values?e.values[t].label:t;if("integer"==e.type||"float"==e.type)throw"should not work for numeric term";throw"unknown term type"}(e[r],a,n,t.ds),delete e[o],l!==r&&(e[l]=e[r],delete e[r])}}}function v(t,e,n=""){if(!t.values||!e.computableValuesOnly)return{values:[],clause:""};const r=Object.keys(t.values).filter((e=>t.values[e].uncomputable)),o=n?`${n}.value`:"value";return{values:r,clause:r.length?`AND ${o} NOT IN (${r.map((()=>"?")).join(",")})`:""}}function b(t,e){if(e.groupsetting&&!e.groupsetting.disabled&&e.groupsetting.inuse){if(Number.isInteger(e.groupsetting.predefined_groupset_idx)){if(e.groupsetting.predefined_groupset_idx<0)throw"q.predefined_groupset_idx out of bound";if(!t.groupsetting)throw"term.groupsetting missing when q.predefined_groupset_idx in use";if(!t.groupsetting.lst)throw"term.groupsetting.lst missing when q.predefined_groupset_idx in use";const n=t.groupsetting.lst[e.groupsetting.predefined_groupset_idx];if(!n)throw"q.predefined_groupset_idx out of bound";return n}if(e.groupsetting.customset)return e.groupsetting.customset;throw"do not know how to get groupset"}}function _(t,e,n,r,i){if("continuous"!=t.mode&&"spline"!=t.mode)return o.compute_bins(t,(t=>x(n,e,i,t)))}async function w(t,e,n,o=!1){const s="string"==typeof t.filter?JSON.parse(decodeURIComponent(t.filter)):t.filter;"integer"!=e.type&&"float"!=e.type||a.lst.find((t=>t.term.id==e.id&&"ranges"in t))||a.lst.push({type:"tvs",tvs:{term:e,ranges:_(t,e,n)}});const a=await i(s,n),l=[];a&&l.push(...a.values);const c=e.values?Object.keys(e.values).filter((t=>e.values[t].uncomputable)):[],u=`${a?"WITH "+a.filters+" ":""}\n\t\tSELECT value\n\t\tFROM anno_${e.type}\n\t\tWHERE\n\t\t${a?"sample IN "+a.CTEname+" AND ":""}\n\t\tterm_id=?\n\t\t${c.length?"AND value NOT IN ("+c.join(",")+")":""}`;l.push(e.id);const f=n.cohort.db.connection.prepare(u).all(l);if(!f.length)return null;f.sort(((t,e)=>t.value-e.value));const d=r.boxplot_getvalue(f);d.mean=f.length?f.reduce(((t,e)=>t+e.value),0)/f.length:0;let h=0;for(const t of f)h+=Math.pow(t.value-d.mean,2);return d.sd=Math.sqrt(h/(f.length-1)),d.min=f[0].value,d.max=f[f.length-1].value,o&&(d.values=f.map((t=>t.value))),d}function x(t,e,n,r=[]){const o=[];n&&o.push(...n.values),o.push(e.id);const i=e.values?Object.keys(e.values).filter((t=>e.values[t].uncomputable)):[],s=[],a=[],l=[];let c;for(const t of r)c="pct_"+t,s.push(`\n\t\t${c} AS (\n\t\t SELECT value\n\t\t FROM vals\n\t\t LIMIT 1\n\t\t OFFSET (\n\t\t SELECT cast ( x as int ) - ( x < cast ( x as int ))\n\t\t FROM (\n\t\t SELECT cast(?*pct as int) as x \n\t\t FROM p\n\t\t )\n\t\t )\n\t\t)`),o.push(t),a.push(c),l.push(`${c}.value AS ${"p"+t}`);const u=`WITH\n\t\t${n?n.filters+", ":""} \n\t\tvals AS (\n\t\t\tSELECT value\n\t\t\tFROM anno_${e.type}\n\t\t\tWHERE\n\t\t\t${n?"sample IN "+n.CTEname+" AND ":""}\n\t\t\tterm_id=?\n\t\t\t${i.length?"AND value NOT IN ("+i.join(",")+")":""}\n\t\t\tORDER BY value ASC\n\t\t),\n\t\tp AS (\n\t\t\tSELECT count(value)/100 as pct\n\t\t\tFROM vals\n\t\t)\n\t\t${s.length?",\n"+s.join(","):""}\n\t\tSELECT \n\t\t\tmin(vals.value) as vmin,\n\t\t\tmax(vals.value) as vmax\n\t\t\t${l.length?",\n"+l.join(",\n"):""} \n\t\tFROM vals ${a.length?","+a.join(","):""}`,f=t.cohort.db.connection.prepare(u).all(o),d=f.length?f[0]:{};return d.max=f[0].vmax,d.min=f[0].vmin,d}function k(t,e){const n=e.slice();let r;return t.split("").map((t=>{if("?"==t){r=t;const e=n.shift();return"string"==typeof e?`'${e}'`:e}return"\t"==t?"":"\n"!=t&&" "!=t||r!==t?(r=t,t):""})).join("")}},827:(t,e,n)=>{"use strict";n.r(e),n.d(e,{binary:()=>a,continuous:()=>o,cubicSpline:()=>i,discrete:()=>s});var r=n(2852);const o={getCTE(t,e,n,o,i,s,a){i.push(e.id);const l=(0,r.getUncomputableClause)(e,o);return i.push(...l.values),{sql:`${t} AS (\n\t\t\t\tSELECT \n\t\t\t\t\tsample,\n\t\t\t\t\tvalue as key, \n\t\t\t\t\tvalue\n\t\t\t\tFROM anno_${e.type}\n\t\t\t\tWHERE term_id=? ${l.clause}\n\t\t\t)`,tablename:t}}},i=o,s={getCTE(t,e,n,o,i,s,a){i.push(e.id);const l=(0,r.get_bins)(o,e,n,s,a),c=[],u=new Map;o.bin_size;for(const t of l)!("name"in t)&&t.label&&(t.name=t.label),u.set(t.name,t),c.push(`SELECT '${t.name}' AS name,\n\t\t\t\t${null==t.start?0:t.start} AS start,\n\t\t\t\t${null==t.stop?0:t.stop} AS stop,\n\t\t\t\t0 AS unannotated,\n\t\t\t\t${t.startunbounded?1:0} AS startunbounded,\n\t\t\t\t${t.stopunbounded?1:0} AS stopunbounded,\n\t\t\t\t${t.startinclusive?1:0} AS startinclusive,\n\t\t\t\t${t.stopinclusive?1:0} AS stopinclusive`);const f=[];if(e.values)for(const t in e.values){const n=e.values[t].uncomputable;if(o.computableValuesOnly&&n)continue;if(!o.computableValuesOnly&&!n)continue;f.push(t);const r=e.values[t];c.push(`SELECT '${r.label}' AS name,\n\t ${t} AS start,\n\t 0 AS stop,\n\t 1 AS unannotated,\n\t 0 AS startunbounded,\n\t 0 AS stopunbounded,\n\t 0 AS startinclusive,\n\t 0 AS stopinclusive`),u.set(r.label,{is_unannotated:!0,value:t,label:r.label})}const d="bin_defs_"+s,h=(0,r.getUncomputableClause)(e,o,"a");i.push(...h.values);return{sql:`${d} AS (\n\t\t\t\t${c.join("\nUNION 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Array(3).concat("fde0ddfa9fb5c51b8a","feebe2fbb4b9f768a1ae017e","feebe2fbb4b9f768a1c51b8a7a0177","feebe2fcc5c0fa9fb5f768a1c51b8a7a0177","feebe2fcc5c0fa9fb5f768a1dd3497ae017e7a0177","fff7f3fde0ddfcc5c0fa9fb5f768a1dd3497ae017e7a0177","fff7f3fde0ddfcc5c0fa9fb5f768a1dd3497ae017e7a017749006a").map(r);const V=m(H);var Y=new Array(3).concat("edf8b17fcdbb2c7fb8","ffffcca1dab441b6c4225ea8","ffffcca1dab441b6c42c7fb8253494","ffffccc7e9b47fcdbb41b6c42c7fb8253494","ffffccc7e9b47fcdbb41b6c41d91c0225ea80c2c84","ffffd9edf8b1c7e9b47fcdbb41b6c41d91c0225ea80c2c84","ffffd9edf8b1c7e9b47fcdbb41b6c41d91c0225ea8253494081d58").map(r);const Q=m(Y);var K=new Array(3).concat("f7fcb9addd8e31a354","ffffccc2e69978c679238443","ffffccc2e69978c67931a354006837","ffffccd9f0a3addd8e78c67931a354006837","ffffccd9f0a3addd8e78c67941ab5d238443005a32","ffffe5f7fcb9d9f0a3addd8e78c67941ab5d238443005a32","ffffe5f7fcb9d9f0a3addd8e78c67941ab5d238443006837004529").map(r);const X=m(K);var tt=new 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t=0,e=this._hullStart;t<q;t++)this.hull[t]=e,e=n[e];this.triangles=this._triangles.subarray(0,this.trianglesLen),this.halfedges=this._halfedges.subarray(0,this.trianglesLen)}_hashKey(t,e){return Math.floor(function(t,e){const n=t/(Math.abs(t)+Math.abs(e));return(e>0?3-n:1+n)/4}(t-this._cx,e-this._cy)*this._hashSize)%this._hashSize}_legalize(t){const{_triangles:e,_halfedges:n,coords:r}=this;let o=0,i=0;for(;;){const s=n[t],a=t-t%3;if(i=a+(t+2)%3,-1===s){if(0===o)break;t=Qr[--o];continue}const l=s-s%3,c=a+(t+1)%3,u=l+(s+2)%3,f=e[i],d=e[t],h=e[c],p=e[u];if(to(r[2*f],r[2*f+1],r[2*d],r[2*d+1],r[2*h],r[2*h+1],r[2*p],r[2*p+1])){e[t]=p,e[s]=f;const r=n[u];if(-1===r){let e=this._hullStart;do{if(this._hullTri[e]===u){this._hullTri[e]=t;break}e=this._hullPrev[e]}while(e!==this._hullStart)}this._link(t,r),this._link(s,n[i]),this._link(i,u);const a=l+(s+1)%3;o<Qr.length&&(Qr[o++]=a)}else{if(0===o)break;t=Qr[--o]}}return i}_link(t,e){this._halfedges[t]=e,-1!==e&&(this._halfedges[e]=t)}_addTriangle(t,e,n,r,o,i){const s=this.trianglesLen;return this._triangles[s]=t,this._triangles[s+1]=e,this._triangles[s+2]=n,this._link(s,r),this._link(s+1,o),this._link(s+2,i),this.trianglesLen+=3,s}}function Xr(t,e,n,r){const o=t-n,i=e-r;return o*o+i*i}function to(t,e,n,r,o,i,s,a){const l=t-s,c=e-a,u=n-s,f=r-a,d=o-s,h=i-a,p=u*u+f*f,m=d*d+h*h;return l*(f*m-p*h)-c*(u*m-p*d)+(l*l+c*c)*(u*h-f*d)<0}function eo(t,e,n,r,o,i){const s=n-t,a=r-e,l=o-t,c=i-e,u=s*s+a*a,f=l*l+c*c,d=.5/(s*c-a*l),h=(c*u-a*f)*d,p=(s*f-l*u)*d;return h*h+p*p}function no(t,e,n,r){if(r-n<=20)for(let o=n+1;o<=r;o++){const r=t[o],i=e[r];let s=o-1;for(;s>=n&&e[t[s]]>i;)t[s+1]=t[s--];t[s+1]=r}else{let o=n+1,i=r;ro(t,n+r>>1,o),e[t[n]]>e[t[r]]&&ro(t,n,r),e[t[o]]>e[t[r]]&&ro(t,o,r),e[t[n]]>e[t[o]]&&ro(t,n,o);const s=t[o],a=e[s];for(;;){do{o++}while(e[t[o]]<a);do{i--}while(e[t[i]]>a);if(i<o)break;ro(t,o,i)}t[n+1]=t[i],t[i]=s,r-o+1>=i-n?(no(t,e,o,r),no(t,e,n,i-1)):(no(t,e,n,i-1),no(t,e,o,r))}}function ro(t,e,n){const r=t[e];t[e]=t[n],t[n]=r}function oo(t){return t[0]}function io(t){return t[1]}const so=1e-6;class ao{constructor(){this._x0=this._y0=this._x1=this._y1=null,this._=""}moveTo(t,e){this._+=`M${this._x0=this._x1=+t},${this._y0=this._y1=+e}`}closePath(){null!==this._x1&&(this._x1=this._x0,this._y1=this._y0,this._+="Z")}lineTo(t,e){this._+=`L${this._x1=+t},${this._y1=+e}`}arc(t,e,n){const r=(t=+t)+(n=+n),o=e=+e;if(n<0)throw new Error("negative radius");null===this._x1?this._+=`M${r},${o}`:(Math.abs(this._x1-r)>so||Math.abs(this._y1-o)>so)&&(this._+="L"+r+","+o),n&&(this._+=`A${n},${n},0,1,1,${t-n},${e}A${n},${n},0,1,1,${this._x1=r},${this._y1=o}`)}rect(t,e,n,r){this._+=`M${this._x0=this._x1=+t},${this._y0=this._y1=+e}h${+n}v${+r}h${-n}Z`}value(){return this._||null}}class lo{constructor(){this._=[]}moveTo(t,e){this._.push([t,e])}closePath(){this._.push(this._[0].slice())}lineTo(t,e){this._.push([t,e])}value(){return this._.length?this._:null}}class co{constructor(t,[e,n,r,o]=[0,0,960,500]){if(!((r=+r)>=(e=+e)&&(o=+o)>=(n=+n)))throw new Error("invalid bounds");this.delaunay=t,this._circumcenters=new Float64Array(2*t.points.length),this.vectors=new Float64Array(2*t.points.length),this.xmax=r,this.xmin=e,this.ymax=o,this.ymin=n,this._init()}update(){return this.delaunay.update(),this._init(),this}_init(){const{delaunay:{points:t,hull:e,triangles:n},vectors:r}=this,o=this.circumcenters=this._circumcenters.subarray(0,n.length/3*2);for(let e,r,i=0,s=0,a=n.length;i<a;i+=3,s+=2){const a=2*n[i],l=2*n[i+1],c=2*n[i+2],u=t[a],f=t[a+1],d=t[l],h=t[l+1],p=t[c],m=t[c+1],g=d-u,y=h-f,v=p-u,b=m-f,_=2*(g*b-y*v);if(Math.abs(_)<1e-9){let o=1e9;const i=2*n[0];o*=Math.sign((t[i]-u)*b-(t[i+1]-f)*v),e=(u+p)/2-o*b,r=(f+m)/2+o*v}else{const t=1/_,n=g*g+y*y,o=v*v+b*b;e=u+(b*n-y*o)*t,r=f+(g*o-v*n)*t}o[s]=e,o[s+1]=r}let i,s,a,l=e[e.length-1],c=4*l,u=t[2*l],f=t[2*l+1];r.fill(0);for(let n=0;n<e.length;++n)l=e[n],i=c,s=u,a=f,c=4*l,u=t[2*l],f=t[2*l+1],r[i+2]=r[c]=a-f,r[i+3]=r[c+1]=u-s}render(t){const e=null==t?t=new ao:void 0,{delaunay:{halfedges:n,inedges:r,hull:o},circumcenters:i,vectors:s}=this;if(o.length<=1)return null;for(let e=0,r=n.length;e<r;++e){const r=n[e];if(r<e)continue;const o=2*Math.floor(e/3),s=2*Math.floor(r/3),a=i[o],l=i[o+1],c=i[s],u=i[s+1];this._renderSegment(a,l,c,u,t)}let a,l=o[o.length-1];for(let e=0;e<o.length;++e){a=l,l=o[e];const n=2*Math.floor(r[l]/3),c=i[n],u=i[n+1],f=4*a,d=this._project(c,u,s[f+2],s[f+3]);d&&this._renderSegment(c,u,d[0],d[1],t)}return e&&e.value()}renderBounds(t){const e=null==t?t=new ao:void 0;return t.rect(this.xmin,this.ymin,this.xmax-this.xmin,this.ymax-this.ymin),e&&e.value()}renderCell(t,e){const n=null==e?e=new ao:void 0,r=this._clip(t);if(null===r||!r.length)return;e.moveTo(r[0],r[1]);let o=r.length;for(;r[0]===r[o-2]&&r[1]===r[o-1]&&o>1;)o-=2;for(let t=2;t<o;t+=2)r[t]===r[t-2]&&r[t+1]===r[t-1]||e.lineTo(r[t],r[t+1]);return e.closePath(),n&&n.value()}*cellPolygons(){const{delaunay:{points:t}}=this;for(let e=0,n=t.length/2;e<n;++e){const t=this.cellPolygon(e);t&&(t.index=e,yield t)}}cellPolygon(t){const e=new lo;return this.renderCell(t,e),e.value()}_renderSegment(t,e,n,r,o){let i;const s=this._regioncode(t,e),a=this._regioncode(n,r);0===s&&0===a?(o.moveTo(t,e),o.lineTo(n,r)):(i=this._clipSegment(t,e,n,r,s,a))&&(o.moveTo(i[0],i[1]),o.lineTo(i[2],i[3]))}contains(t,e,n){return(e=+e)==e&&(n=+n)==n&&this.delaunay._step(t,e,n)===t}*neighbors(t){const e=this._clip(t);if(e)for(const n of this.delaunay.neighbors(t)){const t=this._clip(n);if(t)t:for(let r=0,o=e.length;r<o;r+=2)for(let i=0,s=t.length;i<s;i+=2)if(e[r]==t[i]&&e[r+1]==t[i+1]&&e[(r+2)%o]==t[(i+s-2)%s]&&e[(r+3)%o]==t[(i+s-1)%s]){yield n;break t}}}_cell(t){const{circumcenters:e,delaunay:{inedges:n,halfedges:r,triangles:o}}=this,i=n[t];if(-1===i)return null;const s=[];let a=i;do{const n=Math.floor(a/3);if(s.push(e[2*n],e[2*n+1]),a=a%3==2?a-2:a+1,o[a]!==t)break;a=r[a]}while(a!==i&&-1!==a);return s}_clip(t){if(0===t&&1===this.delaunay.hull.length)return[this.xmax,this.ymin,this.xmax,this.ymax,this.xmin,this.ymax,this.xmin,this.ymin];const e=this._cell(t);if(null===e)return null;const{vectors:n}=this,r=4*t;return n[r]||n[r+1]?this._clipInfinite(t,e,n[r],n[r+1],n[r+2],n[r+3]):this._clipFinite(t,e)}_clipFinite(t,e){const n=e.length;let r,o,i,s,a=null,l=e[n-2],c=e[n-1],u=this._regioncode(l,c),f=0;for(let d=0;d<n;d+=2)if(r=l,o=c,l=e[d],c=e[d+1],i=u,u=this._regioncode(l,c),0===i&&0===u)s=f,f=0,a?a.push(l,c):a=[l,c];else{let e,n,d,h,p;if(0===i){if(null===(e=this._clipSegment(r,o,l,c,i,u)))continue;[n,d,h,p]=e}else{if(null===(e=this._clipSegment(l,c,r,o,u,i)))continue;[h,p,n,d]=e,s=f,f=this._edgecode(n,d),s&&f&&this._edge(t,s,f,a,a.length),a?a.push(n,d):a=[n,d]}s=f,f=this._edgecode(h,p),s&&f&&this._edge(t,s,f,a,a.length),a?a.push(h,p):a=[h,p]}if(a)s=f,f=this._edgecode(a[0],a[1]),s&&f&&this._edge(t,s,f,a,a.length);else if(this.contains(t,(this.xmin+this.xmax)/2,(this.ymin+this.ymax)/2))return[this.xmax,this.ymin,this.xmax,this.ymax,this.xmin,this.ymax,this.xmin,this.ymin];return a}_clipSegment(t,e,n,r,o,i){for(;;){if(0===o&&0===i)return[t,e,n,r];if(o&i)return null;let s,a,l=o||i;8&l?(s=t+(n-t)*(this.ymax-e)/(r-e),a=this.ymax):4&l?(s=t+(n-t)*(this.ymin-e)/(r-e),a=this.ymin):2&l?(a=e+(r-e)*(this.xmax-t)/(n-t),s=this.xmax):(a=e+(r-e)*(this.xmin-t)/(n-t),s=this.xmin),o?(t=s,e=a,o=this._regioncode(t,e)):(n=s,r=a,i=this._regioncode(n,r))}}_clipInfinite(t,e,n,r,o,i){let s,a=Array.from(e);if((s=this._project(a[0],a[1],n,r))&&a.unshift(s[0],s[1]),(s=this._project(a[a.length-2],a[a.length-1],o,i))&&a.push(s[0],s[1]),a=this._clipFinite(t,a))for(let e,n=0,r=a.length,o=this._edgecode(a[r-2],a[r-1]);n<r;n+=2)e=o,o=this._edgecode(a[n],a[n+1]),e&&o&&(n=this._edge(t,e,o,a,n),r=a.length);else this.contains(t,(this.xmin+this.xmax)/2,(this.ymin+this.ymax)/2)&&(a=[this.xmin,this.ymin,this.xmax,this.ymin,this.xmax,this.ymax,this.xmin,this.ymax]);return a}_edge(t,e,n,r,o){for(;e!==n;){let n,i;switch(e){case 5:e=4;continue;case 4:e=6,n=this.xmax,i=this.ymin;break;case 6:e=2;continue;case 2:e=10,n=this.xmax,i=this.ymax;break;case 10:e=8;continue;case 8:e=9,n=this.xmin,i=this.ymax;break;case 9:e=1;continue;case 1:e=5,n=this.xmin,i=this.ymin}r[o]===n&&r[o+1]===i||!this.contains(t,n,i)||(r.splice(o,0,n,i),o+=2)}if(r.length>4)for(let t=0;t<r.length;t+=2){const e=(t+2)%r.length,n=(t+4)%r.length;(r[t]===r[e]&&r[e]===r[n]||r[t+1]===r[e+1]&&r[e+1]===r[n+1])&&(r.splice(e,2),t-=2)}return o}_project(t,e,n,r){let o,i,s,a=1/0;if(r<0){if(e<=this.ymin)return null;(o=(this.ymin-e)/r)<a&&(s=this.ymin,i=t+(a=o)*n)}else if(r>0){if(e>=this.ymax)return null;(o=(this.ymax-e)/r)<a&&(s=this.ymax,i=t+(a=o)*n)}if(n>0){if(t>=this.xmax)return null;(o=(this.xmax-t)/n)<a&&(i=this.xmax,s=e+(a=o)*r)}else if(n<0){if(t<=this.xmin)return null;(o=(this.xmin-t)/n)<a&&(i=this.xmin,s=e+(a=o)*r)}return[i,s]}_edgecode(t,e){return(t===this.xmin?1:t===this.xmax?2:0)|(e===this.ymin?4:e===this.ymax?8:0)}_regioncode(t,e){return(t<this.xmin?1:t>this.xmax?2:0)|(e<this.ymin?4:e>this.ymax?8:0)}}const uo=2*Math.PI,fo=Math.pow;function ho(t){return t[0]}function po(t){return t[1]}function mo(t,e,n){return[t+Math.sin(t+e)*n,e+Math.cos(t-e)*n]}class go{static from(t,e=ho,n=po,r){return new go("length"in t?function(t,e,n,r){const o=t.length,i=new Float64Array(2*o);for(let s=0;s<o;++s){const o=t[s];i[2*s]=e.call(r,o,s,t),i[2*s+1]=n.call(r,o,s,t)}return i}(t,e,n,r):Float64Array.from(function*(t,e,n,r){let o=0;for(const i of t)yield e.call(r,i,o,t),yield n.call(r,i,o,t),++o}(t,e,n,r)))}constructor(t){this._delaunator=new Kr(t),this.inedges=new Int32Array(t.length/2),this._hullIndex=new Int32Array(t.length/2),this.points=this._delaunator.coords,this._init()}update(){return this._delaunator.update(),this._init(),this}_init(){const t=this._delaunator,e=this.points;if(t.hull&&t.hull.length>2&&function(t){const{triangles:e,coords:n}=t;for(let t=0;t<e.length;t+=3){const r=2*e[t],o=2*e[t+1],i=2*e[t+2];if((n[i]-n[r])*(n[o+1]-n[r+1])-(n[o]-n[r])*(n[i+1]-n[r+1])>1e-10)return!1}return!0}(t)){this.collinear=Int32Array.from({length:e.length/2},((t,e)=>e)).sort(((t,n)=>e[2*t]-e[2*n]||e[2*t+1]-e[2*n+1]));const t=this.collinear[0],n=this.collinear[this.collinear.length-1],r=[e[2*t],e[2*t+1],e[2*n],e[2*n+1]],o=1e-8*Math.hypot(r[3]-r[1],r[2]-r[0]);for(let t=0,n=e.length/2;t<n;++t){const n=mo(e[2*t],e[2*t+1],o);e[2*t]=n[0],e[2*t+1]=n[1]}this._delaunator=new Kr(e)}else delete this.collinear;const n=this.halfedges=this._delaunator.halfedges,r=this.hull=this._delaunator.hull,o=this.triangles=this._delaunator.triangles,i=this.inedges.fill(-1),s=this._hullIndex.fill(-1);for(let t=0,e=n.length;t<e;++t){const e=o[t%3==2?t-2:t+1];-1!==n[t]&&-1!==i[e]||(i[e]=t)}for(let t=0,e=r.length;t<e;++t)s[r[t]]=t;r.length<=2&&r.length>0&&(this.triangles=new Int32Array(3).fill(-1),this.halfedges=new Int32Array(3).fill(-1),this.triangles[0]=r[0],i[r[0]]=1,2===r.length&&(i[r[1]]=0,this.triangles[1]=r[1],this.triangles[2]=r[1]))}voronoi(t){return new co(this,t)}*neighbors(t){const{inedges:e,hull:n,_hullIndex:r,halfedges:o,triangles:i,collinear:s}=this;if(s){const e=s.indexOf(t);return e>0&&(yield s[e-1]),void(e<s.length-1&&(yield s[e+1]))}const a=e[t];if(-1===a)return;let l=a,c=-1;do{if(yield c=i[l],l=l%3==2?l-2:l+1,i[l]!==t)return;if(l=o[l],-1===l){const e=n[(r[t]+1)%n.length];return void(e!==c&&(yield e))}}while(l!==a)}find(t,e,n=0){if((t=+t)!=t||(e=+e)!=e)return-1;const r=n;let o;for(;(o=this._step(n,t,e))>=0&&o!==n&&o!==r;)n=o;return o}_step(t,e,n){const{inedges:r,hull:o,_hullIndex:i,halfedges:s,triangles:a,points:l}=this;if(-1===r[t]||!l.length)return(t+1)%(l.length>>1);let c=t,u=fo(e-l[2*t],2)+fo(n-l[2*t+1],2);const f=r[t];let d=f;do{let r=a[d];const f=fo(e-l[2*r],2)+fo(n-l[2*r+1],2);if(f<u&&(u=f,c=r),d=d%3==2?d-2:d+1,a[d]!==t)break;if(d=s[d],-1===d){if(d=o[(i[t]+1)%o.length],d!==r&&fo(e-l[2*d],2)+fo(n-l[2*d+1],2)<u)return d;break}}while(d!==f);return c}render(t){const e=null==t?t=new ao:void 0,{points:n,halfedges:r,triangles:o}=this;for(let e=0,i=r.length;e<i;++e){const i=r[e];if(i<e)continue;const s=2*o[e],a=2*o[i];t.moveTo(n[s],n[s+1]),t.lineTo(n[a],n[a+1])}return this.renderHull(t),e&&e.value()}renderPoints(t,e){void 0!==e||t&&"function"==typeof t.moveTo||(e=t,t=null),e=null==e?2:+e;const n=null==t?t=new ao:void 0,{points:r}=this;for(let 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r=t.invertX(e[0][0])-n[0][0],o=t.invertX(e[1][0])-n[1][0],i=t.invertY(e[0][1])-n[0][1],s=t.invertY(e[1][1])-n[1][1];return t.translate(o>r?(r+o)/2:Math.min(0,r)||Math.max(0,o),s>i?(i+s)/2:Math.min(0,i)||Math.max(0,s))}function rm(){var t,e,n,r=Qp,o=Kp,i=nm,s=tm,a=em,l=[0,1/0],c=[[-1/0,-1/0],[1/0,1/0]],u=250,f=$p.Z,d=N("start","zoom","end"),h=500,p=150,m=0,g=10;function y(t){t.property("__zoom",Xp).on("wheel.zoom",q,{passive:!1}).on("mousedown.zoom",S).on("dblclick.zoom",A).filter(a).on("touchstart.zoom",M).on("touchmove.zoom",T).on("touchend.zoom touchcancel.zoom",C).style("-webkit-tap-highlight-color","rgba(0,0,0,0)")}function v(t,e){return(e=Math.max(l[0],Math.min(l[1],e)))===t.k?t:new Jp(e,t.x,t.y)}function b(t,e,n){var r=e[0]-n[0]*t.k,o=e[1]-n[1]*t.k;return r===t.x&&o===t.y?t:new Jp(t.k,r,o)}function _(t){return[(+t[0][0]+ +t[1][0])/2,(+t[0][1]+ +t[1][1])/2]}function w(t,e,n,r){t.on("start.zoom",(function(){x(this,arguments).event(r).start()})).on("interrupt.zoom end.zoom",(function(){x(this,arguments).event(r).end()})).tween("zoom",(function(){var t=this,i=arguments,s=x(t,i).event(r),a=o.apply(t,i),l=null==n?_(a):"function"==typeof n?n.apply(t,i):n,c=Math.max(a[1][0]-a[0][0],a[1][1]-a[0][1]),u=t.__zoom,d="function"==typeof e?e.apply(t,i):e,h=f(u.invert(l).concat(c/u.k),d.invert(l).concat(c/d.k));return function(t){if(1===t)t=d;else{var e=h(t),n=c/e[2];t=new Jp(n,l[0]-e[0]*n,l[1]-e[1]*n)}s.zoom(null,t)}}))}function x(t,e,n){return!n&&t.__zooming||new k(t,e)}function k(t,e){this.that=t,this.args=e,this.active=0,this.sourceEvent=null,this.extent=o.apply(t,e),this.taps=0}function q(t,...e){if(r.apply(this,arguments)){var n=x(this,e).event(t),o=this.__zoom,a=Math.max(l[0],Math.min(l[1],o.k*Math.pow(2,s.apply(this,arguments)))),u=Ht(t);if(n.wheel)n.mouse[0][0]===u[0]&&n.mouse[0][1]===u[1]||(n.mouse[1]=o.invert(n.mouse[0]=u)),clearTimeout(n.wheel);else{if(o.k===a)return;n.mouse=[u,o.invert(u)],Me(this),n.start()}Yp(t),n.wheel=setTimeout((function(){n.wheel=null,n.end()}),p),n.zoom("mouse",i(b(v(o,a),n.mouse[0],n.mouse[1]),n.extent,c))}}function S(t,...e){if(!n&&r.apply(this,arguments)){var o=t.currentTarget,s=x(this,e,!0).event(t),a=Dt(t.view).on("mousemove.zoom",(function(t){if(Yp(t),!s.moved){var e=t.clientX-u,n=t.clientY-f;s.moved=e*e+n*n>m}s.event(t).zoom("mouse",i(b(s.that.__zoom,s.mouse[0]=Ht(t,o),s.mouse[1]),s.extent,c))}),!0).on("mouseup.zoom",(function(t){a.on("mousemove.zoom mouseup.zoom",null),Ut(t.view,s.moved),Yp(t),s.event(t).end()}),!0),l=Ht(t,o),u=t.clientX,f=t.clientY;Gt(t.view),Vp(t),s.mouse=[l,this.__zoom.invert(l)],Me(this),s.start()}}function A(t,...e){if(r.apply(this,arguments)){var n=this.__zoom,s=Ht(t.changedTouches?t.changedTouches[0]:t,this),a=n.invert(s),l=n.k*(t.shiftKey?.5:2),f=i(b(v(n,l),s,a),o.apply(this,e),c);Yp(t),u>0?Dt(this).transition().duration(u).call(w,f,s,t):Dt(this).call(y.transform,f,s,t)}}function M(n,...o){if(r.apply(this,arguments)){var i,s,a,l,c=n.touches,u=c.length,f=x(this,o,n.changedTouches.length===u).event(n);for(Vp(n),s=0;s<u;++s)l=[l=Ht(a=c[s],this),this.__zoom.invert(l),a.identifier],f.touch0?f.touch1||f.touch0[2]===l[2]||(f.touch1=l,f.taps=0):(f.touch0=l,i=!0,f.taps=1+!!t);t&&(t=clearTimeout(t)),i&&(f.taps<2&&(e=l[0],t=setTimeout((function(){t=null}),h)),Me(this),f.start())}}function T(t,...e){if(this.__zooming){var n,r,o,s,a=x(this,e).event(t),l=t.changedTouches,u=l.length;for(Yp(t),n=0;n<u;++n)o=Ht(r=l[n],this),a.touch0&&a.touch0[2]===r.identifier?a.touch0[0]=o:a.touch1&&a.touch1[2]===r.identifier&&(a.touch1[0]=o);if(r=a.that.__zoom,a.touch1){var f=a.touch0[0],d=a.touch0[1],h=a.touch1[0],p=a.touch1[1],m=(m=h[0]-f[0])*m+(m=h[1]-f[1])*m,g=(g=p[0]-d[0])*g+(g=p[1]-d[1])*g;r=v(r,Math.sqrt(m/g)),o=[(f[0]+h[0])/2,(f[1]+h[1])/2],s=[(d[0]+p[0])/2,(d[1]+p[1])/2]}else{if(!a.touch0)return;o=a.touch0[0],s=a.touch0[1]}a.zoom("touch",i(b(r,o,s),a.extent,c))}}function C(t,...r){if(this.__zooming){var o,i,s=x(this,r).event(t),a=t.changedTouches,l=a.length;for(Vp(t),n&&clearTimeout(n),n=setTimeout((function(){n=null}),h),o=0;o<l;++o)i=a[o],s.touch0&&s.touch0[2]===i.identifier?delete s.touch0:s.touch1&&s.touch1[2]===i.identifier&&delete s.touch1;if(s.touch1&&!s.touch0&&(s.touch0=s.touch1,delete s.touch1),s.touch0)s.touch0[1]=this.__zoom.invert(s.touch0[0]);else if(s.end(),2===s.taps&&(i=Ht(i,this),Math.hypot(e[0]-i[0],e[1]-i[1])<g)){var c=Dt(this).on("dblclick.zoom");c&&c.apply(this,arguments)}}}return y.transform=function(t,e,n,r){var o=t.selection?t.selection():t;o.property("__zoom",Xp),t!==o?w(t,e,n,r):o.interrupt().each((function(){x(this,arguments).event(r).start().zoom(null,"function"==typeof e?e.apply(this,arguments):e).end()}))},y.scaleBy=function(t,e,n,r){y.scaleTo(t,(function(){return this.__zoom.k*("function"==typeof e?e.apply(this,arguments):e)}),n,r)},y.scaleTo=function(t,e,n,r){y.transform(t,(function(){var t=o.apply(this,arguments),r=this.__zoom,s=null==n?_(t):"function"==typeof n?n.apply(this,arguments):n,a=r.invert(s),l="function"==typeof e?e.apply(this,arguments):e;return i(b(v(r,l),s,a),t,c)}),n,r)},y.translateBy=function(t,e,n,r){y.transform(t,(function(){return i(this.__zoom.translate("function"==typeof e?e.apply(this,arguments):e,"function"==typeof n?n.apply(this,arguments):n),o.apply(this,arguments),c)}),null,r)},y.translateTo=function(t,e,n,r,s){y.transform(t,(function(){var t=o.apply(this,arguments),s=this.__zoom,a=null==r?_(t):"function"==typeof r?r.apply(this,arguments):r;return 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arguments.length?(r="function"==typeof t?t:Gp(!!t),y):r},y.touchable=function(t){return arguments.length?(a="function"==typeof t?t:Gp(!!t),y):a},y.extent=function(t){return arguments.length?(o="function"==typeof t?t:Gp([[+t[0][0],+t[0][1]],[+t[1][0],+t[1][1]]]),y):o},y.scaleExtent=function(t){return arguments.length?(l[0]=+t[0],l[1]=+t[1],y):[l[0],l[1]]},y.translateExtent=function(t){return arguments.length?(c[0][0]=+t[0][0],c[1][0]=+t[1][0],c[0][1]=+t[0][1],c[1][1]=+t[1][1],y):[[c[0][0],c[0][1]],[c[1][0],c[1][1]]]},y.constrain=function(t){return arguments.length?(i=t,y):i},y.duration=function(t){return arguments.length?(u=+t,y):u},y.interpolate=function(t){return arguments.length?(f=t,y):f},y.on=function(){var t=d.on.apply(d,arguments);return t===d?y:t},y.clickDistance=function(t){return arguments.length?(m=(t=+t)*t,y):Math.sqrt(m)},y.tapDistance=function(t){return arguments.length?(g=+t,y):g},y}Hp.prototype=Jp.prototype},8828:(t,e,n)=>{"use strict";n.d(e,{H:()=>o,L:()=>r});class r 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